<?xml version="1.0" encoding="UTF-8"?>

<!--XBRL Document Created with the Workiva Platform-->
<!--Copyright 2025 Workiva-->
<!--r:23d99d76-c46c-4660-bb64-5ff1626f1d30,g:cb9f31a4-2bcf-441d-8161-25b117b3acfb-->
<link:linkbase xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd">
  <link:roleRef roleURI="http://www.exelixis.com/role/CONSOLIDATEDBALANCESHEETS" xlink:type="simple" xlink:href="exel-20250103.xsd#CONSOLIDATEDBALANCESHEETS"/>
  <link:calculationLink xlink:role="http://www.exelixis.com/role/CONSOLIDATEDBALANCESHEETS" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_90b9cc73-c691-4318-8017-473c851e47d2" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockholdersEquity"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockValue_843b15d0-1b1b-4944-88fe-6eee6098e37c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PreferredStockValue"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_90b9cc73-c691-4318-8017-473c851e47d2" xlink:to="loc_us-gaap_PreferredStockValue_843b15d0-1b1b-4944-88fe-6eee6098e37c" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockValue_4cc7e163-02d4-4e98-b87b-c605e650d89c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CommonStockValue"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_90b9cc73-c691-4318-8017-473c851e47d2" xlink:to="loc_us-gaap_CommonStockValue_4cc7e163-02d4-4e98-b87b-c605e650d89c" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdditionalPaidInCapital_5a2cbd10-205b-4393-b93a-28786964a502" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AdditionalPaidInCapital"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_90b9cc73-c691-4318-8017-473c851e47d2" xlink:to="loc_us-gaap_AdditionalPaidInCapital_5a2cbd10-205b-4393-b93a-28786964a502" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax_cd7ebedc-b286-4eb3-b6a1-16bf5604297f" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_90b9cc73-c691-4318-8017-473c851e47d2" xlink:to="loc_us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax_cd7ebedc-b286-4eb3-b6a1-16bf5604297f" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RetainedEarningsAccumulatedDeficit_0abde72f-4051-4666-8e89-4c680b9ed80a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RetainedEarningsAccumulatedDeficit"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_90b9cc73-c691-4318-8017-473c851e47d2" xlink:to="loc_us-gaap_RetainedEarningsAccumulatedDeficit_0abde72f-4051-4666-8e89-4c680b9ed80a" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsCurrent_23e71714-5c6b-4a54-8c7a-cb6ad9c109a5" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AssetsCurrent"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ReceivablesNetCurrent_1ca541d4-211d-4f99-8253-2d49efd41b02" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ReceivablesNetCurrent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_23e71714-5c6b-4a54-8c7a-cb6ad9c109a5" xlink:to="loc_us-gaap_ReceivablesNetCurrent_1ca541d4-211d-4f99-8253-2d49efd41b02" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MarketableSecuritiesCurrent_8a4ff504-fb36-4e9d-b76b-7751adb3d582" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_MarketableSecuritiesCurrent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_23e71714-5c6b-4a54-8c7a-cb6ad9c109a5" xlink:to="loc_us-gaap_MarketableSecuritiesCurrent_8a4ff504-fb36-4e9d-b76b-7751adb3d582" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryNet_ab451671-8b54-4601-985f-b60ab7485060" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InventoryNet"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_23e71714-5c6b-4a54-8c7a-cb6ad9c109a5" xlink:to="loc_us-gaap_InventoryNet_ab451671-8b54-4601-985f-b60ab7485060" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsAtCarryingValue_9587bbe1-0671-40a4-acfa-abc55cede264" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CashAndCashEquivalentsAtCarryingValue"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_23e71714-5c6b-4a54-8c7a-cb6ad9c109a5" xlink:to="loc_us-gaap_CashAndCashEquivalentsAtCarryingValue_9587bbe1-0671-40a4-acfa-abc55cede264" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PrepaidExpenseAndOtherAssetsCurrent_a628e2dc-bc43-4978-8b66-6aaa863ade22" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PrepaidExpenseAndOtherAssetsCurrent"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_23e71714-5c6b-4a54-8c7a-cb6ad9c109a5" xlink:to="loc_us-gaap_PrepaidExpenseAndOtherAssetsCurrent_a628e2dc-bc43-4978-8b66-6aaa863ade22" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Assets_117eee5b-28e3-418a-912e-096bda4ebb91" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_Assets"/>
    <link:loc xlink:type="locator" xlink:label="loc_exel_OperatingLeaseRightOfUseAssetAndOtherNonCurrentAssets_fd6c79b9-89dc-4c83-8be4-852cb5b8be27" xlink:href="exel-20250103.xsd#exel_OperatingLeaseRightOfUseAssetAndOtherNonCurrentAssets"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_117eee5b-28e3-418a-912e-096bda4ebb91" xlink:to="loc_exel_OperatingLeaseRightOfUseAssetAndOtherNonCurrentAssets_fd6c79b9-89dc-4c83-8be4-852cb5b8be27" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsCurrent_f9e55b31-7f4e-4c1a-9d47-c1edbca166d0" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AssetsCurrent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_117eee5b-28e3-418a-912e-096bda4ebb91" xlink:to="loc_us-gaap_AssetsCurrent_f9e55b31-7f4e-4c1a-9d47-c1edbca166d0" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Goodwill_5a64492c-ada7-40e5-84df-2027dc1d4686" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_Goodwill"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_117eee5b-28e3-418a-912e-096bda4ebb91" xlink:to="loc_us-gaap_Goodwill_5a64492c-ada7-40e5-84df-2027dc1d4686" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredIncomeTaxAssetsNet_9f393e0b-1de3-4e36-9c31-11f223144de4" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DeferredIncomeTaxAssetsNet"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_117eee5b-28e3-418a-912e-096bda4ebb91" xlink:to="loc_us-gaap_DeferredIncomeTaxAssetsNet_9f393e0b-1de3-4e36-9c31-11f223144de4" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentNet_ad2b62cb-ad22-487d-b103-c4f71fdc8bdc" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PropertyPlantAndEquipmentNet"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_117eee5b-28e3-418a-912e-096bda4ebb91" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentNet_ad2b62cb-ad22-487d-b103-c4f71fdc8bdc" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MarketableSecuritiesNoncurrent_86b3fc2e-7d65-4667-b9d9-2d5d536b49f8" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_MarketableSecuritiesNoncurrent"/>
    <link:calculationArc order="6" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_117eee5b-28e3-418a-912e-096bda4ebb91" xlink:to="loc_us-gaap_MarketableSecuritiesNoncurrent_86b3fc2e-7d65-4667-b9d9-2d5d536b49f8" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesAndStockholdersEquity_d00c01b0-dc1f-4e1f-b3a0-7387fd33fbd1" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LiabilitiesAndStockholdersEquity"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Liabilities_72a93c1f-8f5b-4cfc-ab95-6b310961bf1f" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_Liabilities"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesAndStockholdersEquity_d00c01b0-dc1f-4e1f-b3a0-7387fd33fbd1" xlink:to="loc_us-gaap_Liabilities_72a93c1f-8f5b-4cfc-ab95-6b310961bf1f" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommitmentsAndContingencies_285315db-8f9a-4826-b938-e7ad0eb44393" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CommitmentsAndContingencies"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesAndStockholdersEquity_d00c01b0-dc1f-4e1f-b3a0-7387fd33fbd1" xlink:to="loc_us-gaap_CommitmentsAndContingencies_285315db-8f9a-4826-b938-e7ad0eb44393" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_db2333d7-f545-4e56-9434-875603cd7adc" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockholdersEquity"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesAndStockholdersEquity_d00c01b0-dc1f-4e1f-b3a0-7387fd33fbd1" xlink:to="loc_us-gaap_StockholdersEquity_db2333d7-f545-4e56-9434-875603cd7adc" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesCurrent_6995636c-8e3a-422f-bff5-548ee3ccb459" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LiabilitiesCurrent"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherLiabilitiesCurrent_c71573df-8140-4c56-a52d-ba0492883269" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OtherLiabilitiesCurrent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_6995636c-8e3a-422f-bff5-548ee3ccb459" xlink:to="loc_us-gaap_OtherLiabilitiesCurrent_c71573df-8140-4c56-a52d-ba0492883269" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccruedEmployeeBenefitsCurrent_b6e91a8c-8b4c-4509-b347-6be4d11a5b7d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AccruedEmployeeBenefitsCurrent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_6995636c-8e3a-422f-bff5-548ee3ccb459" xlink:to="loc_us-gaap_AccruedEmployeeBenefitsCurrent_b6e91a8c-8b4c-4509-b347-6be4d11a5b7d" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccountsPayableCurrent_5a87c98a-587a-4807-8b30-651f2de52d63" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AccountsPayableCurrent"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_6995636c-8e3a-422f-bff5-548ee3ccb459" xlink:to="loc_us-gaap_AccountsPayableCurrent_5a87c98a-587a-4807-8b30-651f2de52d63" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CustomerRefundLiabilityCurrent_bfcbc35a-3e2f-422f-8af6-fc218d5b15fc" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CustomerRefundLiabilityCurrent"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_6995636c-8e3a-422f-bff5-548ee3ccb459" xlink:to="loc_us-gaap_CustomerRefundLiabilityCurrent_bfcbc35a-3e2f-422f-8af6-fc218d5b15fc" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_exel_AccruedCollaborationLiabilityCurrent_17569851-2256-421b-b33c-40d6fc97ab9c" xlink:href="exel-20250103.xsd#exel_AccruedCollaborationLiabilityCurrent"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_6995636c-8e3a-422f-bff5-548ee3ccb459" xlink:to="loc_exel_AccruedCollaborationLiabilityCurrent_17569851-2256-421b-b33c-40d6fc97ab9c" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_exel_AccruedClinicalLiabilitiesCurrent_eca809c1-4a0b-4d78-b88f-a15b51a67d0b" xlink:href="exel-20250103.xsd#exel_AccruedClinicalLiabilitiesCurrent"/>
    <link:calculationArc order="6" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_6995636c-8e3a-422f-bff5-548ee3ccb459" xlink:to="loc_exel_AccruedClinicalLiabilitiesCurrent_eca809c1-4a0b-4d78-b88f-a15b51a67d0b" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Liabilities_9d1da57f-af16-4640-8d6d-ddc11e3529d2" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_Liabilities"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesCurrent_347a508c-1272-4b00-9a93-75ce87a64109" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LiabilitiesCurrent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Liabilities_9d1da57f-af16-4640-8d6d-ddc11e3529d2" xlink:to="loc_us-gaap_LiabilitiesCurrent_347a508c-1272-4b00-9a93-75ce87a64109" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseLiabilityNoncurrent_7c90e425-7ef0-45c2-a04a-ba8bf9b7a9c2" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingLeaseLiabilityNoncurrent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Liabilities_9d1da57f-af16-4640-8d6d-ddc11e3529d2" xlink:to="loc_us-gaap_OperatingLeaseLiabilityNoncurrent_7c90e425-7ef0-45c2-a04a-ba8bf9b7a9c2" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherLiabilitiesNoncurrent_6fd8bf23-db72-4410-9ae6-f1e5f447ad69" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OtherLiabilitiesNoncurrent"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Liabilities_9d1da57f-af16-4640-8d6d-ddc11e3529d2" xlink:to="loc_us-gaap_OtherLiabilitiesNoncurrent_6fd8bf23-db72-4410-9ae6-f1e5f447ad69" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.exelixis.com/role/CONSOLIDATEDSTATEMENTSOFINCOME" xlink:type="simple" xlink:href="exel-20250103.xsd#CONSOLIDATEDSTATEMENTSOFINCOME"/>
  <link:calculationLink xlink:role="http://www.exelixis.com/role/CONSOLIDATEDSTATEMENTSOFINCOME" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_a35e9600-a520-4ca9-b662-08180c9b27e8" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetIncomeLoss"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeLossAttributableToParent_849c1c3b-f598-4e45-9471-4729270a3629" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeLossAttributableToParent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetIncomeLoss_a35e9600-a520-4ca9-b662-08180c9b27e8" xlink:to="loc_us-gaap_IncomeLossAttributableToParent_849c1c3b-f598-4e45-9471-4729270a3629" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxExpenseBenefit_acd3f704-c403-4379-bf21-eec1d2cf6274" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeTaxExpenseBenefit"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetIncomeLoss_a35e9600-a520-4ca9-b662-08180c9b27e8" xlink:to="loc_us-gaap_IncomeTaxExpenseBenefit_acd3f704-c403-4379-bf21-eec1d2cf6274" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeLossAttributableToParent_9739af20-f745-44dd-a0f4-9c9536e6e5d0" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeLossAttributableToParent"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingIncomeLoss_12d2059e-c39b-43fa-a7c4-5a33dd5ec3b0" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingIncomeLoss"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_IncomeLossAttributableToParent_9739af20-f745-44dd-a0f4-9c9536e6e5d0" xlink:to="loc_us-gaap_OperatingIncomeLoss_12d2059e-c39b-43fa-a7c4-5a33dd5ec3b0" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestIncomeOther_67e909fb-207a-45d2-b9b8-4886f9f8b401" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InterestIncomeOther"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_IncomeLossAttributableToParent_9739af20-f745-44dd-a0f4-9c9536e6e5d0" xlink:to="loc_us-gaap_InterestIncomeOther_67e909fb-207a-45d2-b9b8-4886f9f8b401" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherNonoperatingIncomeExpense_0385d56b-61e8-430c-b84a-96d4e42270c7" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OtherNonoperatingIncomeExpense"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_IncomeLossAttributableToParent_9739af20-f745-44dd-a0f4-9c9536e6e5d0" xlink:to="loc_us-gaap_OtherNonoperatingIncomeExpense_0385d56b-61e8-430c-b84a-96d4e42270c7" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostsAndExpenses_1df5d724-344b-4ec2-8de9-77a930953e76" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CostsAndExpenses"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ImpairmentOfLongLivedAssetsHeldForUse_16734f98-ae6b-4892-bf4d-c447a68227bd" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ImpairmentOfLongLivedAssetsHeldForUse"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CostsAndExpenses_1df5d724-344b-4ec2-8de9-77a930953e76" xlink:to="loc_us-gaap_ImpairmentOfLongLivedAssetsHeldForUse_16734f98-ae6b-4892-bf4d-c447a68227bd" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SellingGeneralAndAdministrativeExpense_f539fc32-9c49-4c83-8194-b636a91e2361" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SellingGeneralAndAdministrativeExpense"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CostsAndExpenses_1df5d724-344b-4ec2-8de9-77a930953e76" xlink:to="loc_us-gaap_SellingGeneralAndAdministrativeExpense_f539fc32-9c49-4c83-8194-b636a91e2361" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpense_1d4ff771-ef4e-4a6b-913f-7c7f6e238927" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ResearchAndDevelopmentExpense"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CostsAndExpenses_1df5d724-344b-4ec2-8de9-77a930953e76" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpense_1d4ff771-ef4e-4a6b-913f-7c7f6e238927" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringCharges_e5fb68b5-d89b-473e-9bf8-1cab6605299d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RestructuringCharges"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CostsAndExpenses_1df5d724-344b-4ec2-8de9-77a930953e76" xlink:to="loc_us-gaap_RestructuringCharges_e5fb68b5-d89b-473e-9bf8-1cab6605299d" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostOfGoodsAndServicesSold_ca1506cb-f35d-4d8a-9c0e-dc070487e9a7" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CostOfGoodsAndServicesSold"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CostsAndExpenses_1df5d724-344b-4ec2-8de9-77a930953e76" xlink:to="loc_us-gaap_CostOfGoodsAndServicesSold_ca1506cb-f35d-4d8a-9c0e-dc070487e9a7" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingIncomeLoss_1d8781a8-d28d-43d3-9816-8aa558fc8167" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingIncomeLoss"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_95d27ea2-bcfd-41c1-ba8d-22603f1541e9" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_OperatingIncomeLoss_1d8781a8-d28d-43d3-9816-8aa558fc8167" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_95d27ea2-bcfd-41c1-ba8d-22603f1541e9" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostsAndExpenses_86b415dd-b4ce-43b8-99d2-eca2ffd115f4" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CostsAndExpenses"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_OperatingIncomeLoss_1d8781a8-d28d-43d3-9816-8aa558fc8167" xlink:to="loc_us-gaap_CostsAndExpenses_86b415dd-b4ce-43b8-99d2-eca2ffd115f4" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.exelixis.com/role/CONSOLIDATEDSTATEMENTSOFCOMPREHENSIVEINCOME" xlink:type="simple" xlink:href="exel-20250103.xsd#CONSOLIDATEDSTATEMENTSOFCOMPREHENSIVEINCOME"/>
  <link:calculationLink xlink:role="http://www.exelixis.com/role/CONSOLIDATEDSTATEMENTSOFCOMPREHENSIVEINCOME" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ComprehensiveIncomeNetOfTax_00f33747-cba9-47b1-a5cb-ad3802d0f557" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ComprehensiveIncomeNetOfTax"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_f6da4e3f-c7db-408b-a642-7c6125c38ab6" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetIncomeLoss"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_ComprehensiveIncomeNetOfTax_00f33747-cba9-47b1-a5cb-ad3802d0f557" xlink:to="loc_us-gaap_NetIncomeLoss_f6da4e3f-c7db-408b-a642-7c6125c38ab6" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax_abe51548-b187-4cd1-8084-4b92c0a840a7" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_ComprehensiveIncomeNetOfTax_00f33747-cba9-47b1-a5cb-ad3802d0f557" xlink:to="loc_us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax_abe51548-b187-4cd1-8084-4b92c0a840a7" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.exelixis.com/role/CONSOLIDATEDSTATEMENTSOFCASHFLOWS" xlink:type="simple" xlink:href="exel-20250103.xsd#CONSOLIDATEDSTATEMENTSOFCASHFLOWS"/>
  <link:calculationLink xlink:role="http://www.exelixis.com/role/CONSOLIDATEDSTATEMENTSOFCASHFLOWS" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_ead3c937-e3ec-4c1a-9bb5-24aaba9f997e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetCashProvidedByUsedInFinancingActivities"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsForRepurchaseOfCommonStock_be8ea236-9800-4059-b106-8a9e47d3c386" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PaymentsForRepurchaseOfCommonStock"/>
    <link:calculationArc order="1" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_ead3c937-e3ec-4c1a-9bb5-24aaba9f997e" xlink:to="loc_us-gaap_PaymentsForRepurchaseOfCommonStock_be8ea236-9800-4059-b106-8a9e47d3c386" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions_a741f2a8-c2cb-4262-9f55-375e2894353d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_ead3c937-e3ec-4c1a-9bb5-24aaba9f997e" xlink:to="loc_us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions_a741f2a8-c2cb-4262-9f55-375e2894353d" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation_ec79e3b3-3cea-4f31-b3e1-7e469a136f83" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation"/>
    <link:calculationArc order="3" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_ead3c937-e3ec-4c1a-9bb5-24aaba9f997e" xlink:to="loc_us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation_ec79e3b3-3cea-4f31-b3e1-7e469a136f83" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_218c4641-e500-421a-ba7b-c20426d41e1e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_8074b6de-395a-4728-b966-9d0787fa6f38" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetCashProvidedByUsedInOperatingActivities"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_218c4641-e500-421a-ba7b-c20426d41e1e" xlink:to="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_8074b6de-395a-4728-b966-9d0787fa6f38" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_19827859-0e99-4ed8-9274-7715b6310dce" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetCashProvidedByUsedInInvestingActivities"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_218c4641-e500-421a-ba7b-c20426d41e1e" xlink:to="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_19827859-0e99-4ed8-9274-7715b6310dce" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_a225b295-c7b1-4b62-8bdc-7d47e2f61cf5" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetCashProvidedByUsedInFinancingActivities"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_218c4641-e500-421a-ba7b-c20426d41e1e" xlink:to="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_a225b295-c7b1-4b62-8bdc-7d47e2f61cf5" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_c4423f55-fb1a-4a48-bd8f-f32ab6fc1538" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetCashProvidedByUsedInOperatingActivities"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DepreciationDepletionAndAmortization_2b601c32-a193-4529-9aea-aa23d1a3cb00" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DepreciationDepletionAndAmortization"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_c4423f55-fb1a-4a48-bd8f-f32ab6fc1538" xlink:to="loc_us-gaap_DepreciationDepletionAndAmortization_2b601c32-a193-4529-9aea-aa23d1a3cb00" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInDeferredIncomeTaxes_40d759fa-735a-41f5-b9b1-74d4cce83b7a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncreaseDecreaseInDeferredIncomeTaxes"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_c4423f55-fb1a-4a48-bd8f-f32ab6fc1538" xlink:to="loc_us-gaap_IncreaseDecreaseInDeferredIncomeTaxes_40d759fa-735a-41f5-b9b1-74d4cce83b7a" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherNoncashIncomeExpense_ee6710c8-7ab2-4e8d-9abd-1100a7c9b01e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OtherNoncashIncomeExpense"/>
    <link:calculationArc order="3" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_c4423f55-fb1a-4a48-bd8f-f32ab6fc1538" xlink:to="loc_us-gaap_OtherNoncashIncomeExpense_ee6710c8-7ab2-4e8d-9abd-1100a7c9b01e" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets_3b0e1d52-6ea4-4177-8094-3d6b4726669f" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets"/>
    <link:calculationArc order="4" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_c4423f55-fb1a-4a48-bd8f-f32ab6fc1538" xlink:to="loc_us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets_3b0e1d52-6ea4-4177-8094-3d6b4726669f" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_f39db8c3-e5fe-41a0-bc13-d8540261066f" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetIncomeLoss"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_c4423f55-fb1a-4a48-bd8f-f32ab6fc1538" xlink:to="loc_us-gaap_NetIncomeLoss_f39db8c3-e5fe-41a0-bc13-d8540261066f" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentAssetAcquiredOtherThanThroughBusinessCombinationWrittenOff_6903a4f0-b66c-4b80-ba9f-372629687966" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ResearchAndDevelopmentAssetAcquiredOtherThanThroughBusinessCombinationWrittenOff"/>
    <link:calculationArc order="6" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_c4423f55-fb1a-4a48-bd8f-f32ab6fc1538" xlink:to="loc_us-gaap_ResearchAndDevelopmentAssetAcquiredOtherThanThroughBusinessCombinationWrittenOff_6903a4f0-b66c-4b80-ba9f-372629687966" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInInventories_c7678ba3-260a-4339-8f0d-1aa6abd26284" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncreaseDecreaseInInventories"/>
    <link:calculationArc order="7" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_c4423f55-fb1a-4a48-bd8f-f32ab6fc1538" xlink:to="loc_us-gaap_IncreaseDecreaseInInventories_c7678ba3-260a-4339-8f0d-1aa6abd26284" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInAccruedLiabilities_7e5de55e-f26c-4e09-85bc-d28f71b2ae97" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncreaseDecreaseInAccruedLiabilities"/>
    <link:calculationArc order="8" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_c4423f55-fb1a-4a48-bd8f-f32ab6fc1538" xlink:to="loc_us-gaap_IncreaseDecreaseInAccruedLiabilities_7e5de55e-f26c-4e09-85bc-d28f71b2ae97" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringCostsAndAssetImpairmentCharges_f8139be4-3a7d-414b-8028-a070392cd488" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RestructuringCostsAndAssetImpairmentCharges"/>
    <link:calculationArc order="9" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_c4423f55-fb1a-4a48-bd8f-f32ab6fc1538" xlink:to="loc_us-gaap_RestructuringCostsAndAssetImpairmentCharges_f8139be4-3a7d-414b-8028-a070392cd488" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_exel_NoncashLeaseExpense_29eb9dab-e992-485c-8e45-c74658da38d3" xlink:href="exel-20250103.xsd#exel_NoncashLeaseExpense"/>
    <link:calculationArc order="10" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_c4423f55-fb1a-4a48-bd8f-f32ab6fc1538" xlink:to="loc_exel_NoncashLeaseExpense_29eb9dab-e992-485c-8e45-c74658da38d3" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensation_73aca4c8-2b48-44b5-ab13-fac3c08a4425" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensation"/>
    <link:calculationArc order="11" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_c4423f55-fb1a-4a48-bd8f-f32ab6fc1538" xlink:to="loc_us-gaap_ShareBasedCompensation_73aca4c8-2b48-44b5-ab13-fac3c08a4425" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInAccountsPayable_b126ebbf-7903-45fa-9fdf-cbe5e2749ddd" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncreaseDecreaseInAccountsPayable"/>
    <link:calculationArc order="12" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_c4423f55-fb1a-4a48-bd8f-f32ab6fc1538" xlink:to="loc_us-gaap_IncreaseDecreaseInAccountsPayable_b126ebbf-7903-45fa-9fdf-cbe5e2749ddd" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInAccountsReceivable_8a6eb3ee-1d3f-4029-b3b3-98a585d4f791" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncreaseDecreaseInAccountsReceivable"/>
    <link:calculationArc order="13" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_c4423f55-fb1a-4a48-bd8f-f32ab6fc1538" xlink:to="loc_us-gaap_IncreaseDecreaseInAccountsReceivable_8a6eb3ee-1d3f-4029-b3b3-98a585d4f791" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_1d83a2fb-1fa2-4fe5-9742-c1ec2877a0bb" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetCashProvidedByUsedInInvestingActivities"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromSaleAndMaturityOfMarketableSecurities_2cdbd0af-a1f0-4731-9bde-8d59eb9faef5" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ProceedsFromSaleAndMaturityOfMarketableSecurities"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_1d83a2fb-1fa2-4fe5-9742-c1ec2877a0bb" xlink:to="loc_us-gaap_ProceedsFromSaleAndMaturityOfMarketableSecurities_2cdbd0af-a1f0-4731-9bde-8d59eb9faef5" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_2f4c6360-e539-4f1b-aa43-1b4a76eef520" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PaymentsToAcquirePropertyPlantAndEquipment"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_1d83a2fb-1fa2-4fe5-9742-c1ec2877a0bb" xlink:to="loc_us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_2f4c6360-e539-4f1b-aa43-1b4a76eef520" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsToAcquireMarketableSecurities_d5574c83-925d-4bd3-95aa-f19e55a2e963" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PaymentsToAcquireMarketableSecurities"/>
    <link:calculationArc order="3" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_1d83a2fb-1fa2-4fe5-9742-c1ec2877a0bb" xlink:to="loc_us-gaap_PaymentsToAcquireMarketableSecurities_d5574c83-925d-4bd3-95aa-f19e55a2e963" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsToAcquireInProcessResearchAndDevelopment_155e30dc-e6d6-491f-98f8-4dc209f6e911" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PaymentsToAcquireInProcessResearchAndDevelopment"/>
    <link:calculationArc order="4" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_1d83a2fb-1fa2-4fe5-9742-c1ec2877a0bb" xlink:to="loc_us-gaap_PaymentsToAcquireInProcessResearchAndDevelopment_155e30dc-e6d6-491f-98f8-4dc209f6e911" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.exelixis.com/role/SegmentReportingSegmentandConsolidatedNetIncomeDetails" xlink:type="simple" xlink:href="exel-20250103.xsd#SegmentReportingSegmentandConsolidatedNetIncomeDetails"/>
  <link:calculationLink xlink:role="http://www.exelixis.com/role/SegmentReportingSegmentandConsolidatedNetIncomeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_1ceee7f3-3c03-45b6-bd53-5d16d7a42726" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetIncomeLoss"/>
    <link:loc xlink:type="locator" xlink:label="loc_exel_DevelopmentExpenses_e500c9a1-e802-409f-b45c-72805c73bc32" xlink:href="exel-20250103.xsd#exel_DevelopmentExpenses"/>
    <link:calculationArc order="1" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetIncomeLoss_1ceee7f3-3c03-45b6-bd53-5d16d7a42726" xlink:to="loc_exel_DevelopmentExpenses_e500c9a1-e802-409f-b45c-72805c73bc32" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_exel_DrugDiscoveryCosts_24fbcb04-b85d-4784-b2a1-0a8a2cf15919" xlink:href="exel-20250103.xsd#exel_DrugDiscoveryCosts"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetIncomeLoss_1ceee7f3-3c03-45b6-bd53-5d16d7a42726" xlink:to="loc_exel_DrugDiscoveryCosts_24fbcb04-b85d-4784-b2a1-0a8a2cf15919" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxExpenseBenefit_3c6a5c6d-779f-48fa-8138-f174b65d3d44" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeTaxExpenseBenefit"/>
    <link:calculationArc order="3" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetIncomeLoss_1ceee7f3-3c03-45b6-bd53-5d16d7a42726" xlink:to="loc_us-gaap_IncomeTaxExpenseBenefit_3c6a5c6d-779f-48fa-8138-f174b65d3d44" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestIncomeOther_29cfc303-c2a7-4348-a2f0-d60d56ef4d56" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InterestIncomeOther"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetIncomeLoss_1ceee7f3-3c03-45b6-bd53-5d16d7a42726" xlink:to="loc_us-gaap_InterestIncomeOther_29cfc303-c2a7-4348-a2f0-d60d56ef4d56" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_exel_SellingGeneralAndAdministrativeExpenseExcludingSeparateAccounts_97e79574-b7ff-40cf-92d6-de726332857b" xlink:href="exel-20250103.xsd#exel_SellingGeneralAndAdministrativeExpenseExcludingSeparateAccounts"/>
    <link:calculationArc order="5" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetIncomeLoss_1ceee7f3-3c03-45b6-bd53-5d16d7a42726" xlink:to="loc_exel_SellingGeneralAndAdministrativeExpenseExcludingSeparateAccounts_97e79574-b7ff-40cf-92d6-de726332857b" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostOfGoodsAndServicesSold_dde8b8cf-f1d8-4394-91c3-94ba9ff51be6" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CostOfGoodsAndServicesSold"/>
    <link:calculationArc order="6" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetIncomeLoss_1ceee7f3-3c03-45b6-bd53-5d16d7a42726" xlink:to="loc_us-gaap_CostOfGoodsAndServicesSold_dde8b8cf-f1d8-4394-91c3-94ba9ff51be6" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_3b59bc57-b7c9-4e67-b570-1584fa902c26" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:calculationArc order="7" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetIncomeLoss_1ceee7f3-3c03-45b6-bd53-5d16d7a42726" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_3b59bc57-b7c9-4e67-b570-1584fa902c26" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentReportingOtherItemAmount_0d09d182-784d-415d-9c50-99a917c4dd9a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SegmentReportingOtherItemAmount"/>
    <link:calculationArc order="8" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetIncomeLoss_1ceee7f3-3c03-45b6-bd53-5d16d7a42726" xlink:to="loc_us-gaap_SegmentReportingOtherItemAmount_0d09d182-784d-415d-9c50-99a917c4dd9a" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.exelixis.com/role/RevenuesContractAssetsandLiabilitiesDetails" xlink:type="simple" xlink:href="exel-20250103.xsd#RevenuesContractAssetsandLiabilitiesDetails"/>
  <link:calculationLink xlink:role="http://www.exelixis.com/role/RevenuesContractAssetsandLiabilitiesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiability_f3bf9b1d-09c3-49fa-a87f-1cf384ba9691" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ContractWithCustomerLiability"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityCurrent_d4a21e75-911b-475d-af28-037f4732c8bd" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ContractWithCustomerLiabilityCurrent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_ContractWithCustomerLiability_f3bf9b1d-09c3-49fa-a87f-1cf384ba9691" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityCurrent_d4a21e75-911b-475d-af28-037f4732c8bd" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityNoncurrent_2e59eb8c-4795-4013-8b25-7bb9ec956571" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ContractWithCustomerLiabilityNoncurrent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_ContractWithCustomerLiability_f3bf9b1d-09c3-49fa-a87f-1cf384ba9691" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityNoncurrent_2e59eb8c-4795-4013-8b25-7bb9ec956571" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.exelixis.com/role/CashandMarketableSecuritiesInvestmentsbySecurityTypeDetails" xlink:type="simple" xlink:href="exel-20250103.xsd#CashandMarketableSecuritiesInvestmentsbySecurityTypeDetails"/>
  <link:calculationLink xlink:role="http://www.exelixis.com/role/CashandMarketableSecuritiesInvestmentsbySecurityTypeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_exel_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsAndAvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_3caecdc3-ca4f-46bb-8838-cfb21960b7b4" xlink:href="exel-20250103.xsd#exel_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsAndAvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_873c9504-de44-48ab-b710-4f667ffbf811" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_exel_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsAndAvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_3caecdc3-ca4f-46bb-8838-cfb21960b7b4" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_873c9504-de44-48ab-b710-4f667ffbf811" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_exel_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsGrossUnrealizedGain_83cad116-0ee4-46a6-a1e2-3b394fdb66f7" xlink:href="exel-20250103.xsd#exel_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsGrossUnrealizedGain"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_exel_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsAndAvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_3caecdc3-ca4f-46bb-8838-cfb21960b7b4" xlink:to="loc_exel_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsGrossUnrealizedGain_83cad116-0ee4-46a6-a1e2-3b394fdb66f7" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_exel_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsAndAvailableForSaleDebtSecuritiesAmortizedCostBasis_6355dfad-f295-40d2-b3f6-f823191e9b36" xlink:href="exel-20250103.xsd#exel_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsAndAvailableForSaleDebtSecuritiesAmortizedCostBasis"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_81b87103-f577-4897-9c44-fbc5f2a34f5c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_exel_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsAndAvailableForSaleDebtSecuritiesAmortizedCostBasis_6355dfad-f295-40d2-b3f6-f823191e9b36" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_81b87103-f577-4897-9c44-fbc5f2a34f5c" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_exel_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsAmortizedCost_87780fda-15b7-4b4a-9807-ed31269242d6" xlink:href="exel-20250103.xsd#exel_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsAmortizedCost"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_exel_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsAndAvailableForSaleDebtSecuritiesAmortizedCostBasis_6355dfad-f295-40d2-b3f6-f823191e9b36" xlink:to="loc_exel_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsAmortizedCost_87780fda-15b7-4b4a-9807-ed31269242d6" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_2a701fb9-852a-49fa-869c-2de37258a231" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_694f02a2-9de2-4031-934e-15f3aaccd40c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax"/>
    <link:calculationArc order="1" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_2a701fb9-852a-49fa-869c-2de37258a231" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_694f02a2-9de2-4031-934e-15f3aaccd40c" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_448467bc-9b7e-4713-8d02-9b519cdf5be8" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_2a701fb9-852a-49fa-869c-2de37258a231" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_448467bc-9b7e-4713-8d02-9b519cdf5be8" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_14585cf1-c3e2-4bed-a2e3-03d8a4454124" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_2a701fb9-852a-49fa-869c-2de37258a231" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_14585cf1-c3e2-4bed-a2e3-03d8a4454124" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_exel_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsAndAvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_c018a076-e6fa-4a62-b34c-4b028ddd790c" xlink:href="exel-20250103.xsd#exel_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsAndAvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_1d09b707-a99a-4b4c-b1cd-b1ec04f6d5b1" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_exel_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsAndAvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_c018a076-e6fa-4a62-b34c-4b028ddd790c" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_1d09b707-a99a-4b4c-b1cd-b1ec04f6d5b1" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_exel_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsGrossUnrealizedLoss_0cf6a7a9-ff76-4052-a80a-eb6b980662e2" xlink:href="exel-20250103.xsd#exel_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsGrossUnrealizedLoss"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_exel_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsAndAvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_c018a076-e6fa-4a62-b34c-4b028ddd790c" xlink:to="loc_exel_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsGrossUnrealizedLoss_0cf6a7a9-ff76-4052-a80a-eb6b980662e2" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_exel_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsAndAvailableForSaleDebtSecurities_0b4ea48d-1bce-45d4-8b1a-50a42ef793e3" xlink:href="exel-20250103.xsd#exel_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsAndAvailableForSaleDebtSecurities"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_218a99de-8b1a-4382-bbf4-59110c13e3ce" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_exel_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsAndAvailableForSaleDebtSecurities_0b4ea48d-1bce-45d4-8b1a-50a42ef793e3" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_218a99de-8b1a-4382-bbf4-59110c13e3ce" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_exel_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsFairValueDisclosure_9b73afde-9e37-4f10-853d-c662b99b890d" xlink:href="exel-20250103.xsd#exel_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsFairValueDisclosure"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_exel_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsAndAvailableForSaleDebtSecurities_0b4ea48d-1bce-45d4-8b1a-50a42ef793e3" xlink:to="loc_exel_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsFairValueDisclosure_9b73afde-9e37-4f10-853d-c662b99b890d" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_exel_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsAmortizedCost_802582f2-2423-4d81-916e-6007b66409b2" xlink:href="exel-20250103.xsd#exel_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsAmortizedCost"/>
    <link:loc xlink:type="locator" xlink:label="loc_exel_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsGrossUnrealizedGain_30210e65-f2dd-488c-8928-78b7d1df0ce5" xlink:href="exel-20250103.xsd#exel_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsGrossUnrealizedGain"/>
    <link:calculationArc order="1" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_exel_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsAmortizedCost_802582f2-2423-4d81-916e-6007b66409b2" xlink:to="loc_exel_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsGrossUnrealizedGain_30210e65-f2dd-488c-8928-78b7d1df0ce5" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_exel_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsGrossUnrealizedLoss_6043b2fa-5eb8-4970-a5b2-0cc29f93d90a" xlink:href="exel-20250103.xsd#exel_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsGrossUnrealizedLoss"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_exel_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsAmortizedCost_802582f2-2423-4d81-916e-6007b66409b2" xlink:to="loc_exel_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsGrossUnrealizedLoss_6043b2fa-5eb8-4970-a5b2-0cc29f93d90a" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_exel_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsFairValueDisclosure_11269510-1008-4998-a0da-854331033dd0" xlink:href="exel-20250103.xsd#exel_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsFairValueDisclosure"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_exel_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsAmortizedCost_802582f2-2423-4d81-916e-6007b66409b2" xlink:to="loc_exel_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsFairValueDisclosure_11269510-1008-4998-a0da-854331033dd0" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.exelixis.com/role/CashandMarketableSecuritiesFairValueandGrossUnrealizedLossesofInvestmentsAvailableforSaleinanUnrealizedLossPositionDetails" xlink:type="simple" xlink:href="exel-20250103.xsd#CashandMarketableSecuritiesFairValueandGrossUnrealizedLossesofInvestmentsAvailableforSaleinanUnrealizedLossPositionDetails"/>
  <link:calculationLink xlink:role="http://www.exelixis.com/role/CashandMarketableSecuritiesFairValueandGrossUnrealizedLossesofInvestmentsAvailableforSaleinanUnrealizedLossPositionDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition_e070ffe7-496a-4ee8-a609-5d6ae20b55e0" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months_00af169e-33b7-4f32-8f80-c6576e6bb758" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition_e070ffe7-496a-4ee8-a609-5d6ae20b55e0" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months_00af169e-33b7-4f32-8f80-c6576e6bb758" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger_36f07967-f7b0-4a79-a09b-e5ce470b5a46" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition_e070ffe7-496a-4ee8-a609-5d6ae20b55e0" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger_36f07967-f7b0-4a79-a09b-e5ce470b5a46" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss_8f111efa-861a-4d3e-b610-bd97104dd993" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss_3ab4bf33-be4c-4800-815f-770afa0fb50e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss_8f111efa-861a-4d3e-b610-bd97104dd993" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss_3ab4bf33-be4c-4800-815f-770afa0fb50e" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss_f454dfc3-3694-49ea-8d60-3084727f1f28" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss_8f111efa-861a-4d3e-b610-bd97104dd993" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss_f454dfc3-3694-49ea-8d60-3084727f1f28" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.exelixis.com/role/CashandMarketableSecuritiesFairValueofCashEquivalentsandInvestmentsbyContractualMaturityDetails" xlink:type="simple" xlink:href="exel-20250103.xsd#CashandMarketableSecuritiesFairValueofCashEquivalentsandInvestmentsbyContractualMaturityDetails"/>
  <link:calculationLink xlink:role="http://www.exelixis.com/role/CashandMarketableSecuritiesFairValueofCashEquivalentsandInvestmentsbyContractualMaturityDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_f4c0e1b3-e02e-4c46-a1c6-715a9a94b565" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearFairValue_b1a13a0f-0643-4edb-a1c3-e2847c7708da" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearFairValue"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_f4c0e1b3-e02e-4c46-a1c6-715a9a94b565" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearFairValue_b1a13a0f-0643-4edb-a1c3-e2847c7708da" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughFiveYearsFairValue_adaf9e44-1a1e-45ea-a8b5-2217a91b1484" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughFiveYearsFairValue"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_f4c0e1b3-e02e-4c46-a1c6-715a9a94b565" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughFiveYearsFairValue_adaf9e44-1a1e-45ea-a8b5-2217a91b1484" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.exelixis.com/role/FairValueMeasurementsDetails" xlink:type="simple" xlink:href="exel-20250103.xsd#FairValueMeasurementsDetails"/>
  <link:calculationLink xlink:role="http://www.exelixis.com/role/FairValueMeasurementsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsFairValueDisclosure_b5f94295-fc70-4e40-9591-e36b1b8bbf59" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AssetsFairValueDisclosure"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_182bf80f-4574-4748-b009-fc1d7cc93926" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsFairValueDisclosure_b5f94295-fc70-4e40-9591-e36b1b8bbf59" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_182bf80f-4574-4748-b009-fc1d7cc93926" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsFairValueDisclosure_a7a8d18a-3a75-4ff2-bebb-b20d456b81ce" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CashAndCashEquivalentsFairValueDisclosure"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsFairValueDisclosure_b5f94295-fc70-4e40-9591-e36b1b8bbf59" xlink:to="loc_us-gaap_CashAndCashEquivalentsFairValueDisclosure_a7a8d18a-3a75-4ff2-bebb-b20d456b81ce" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.exelixis.com/role/InventoryDetails" xlink:type="simple" xlink:href="exel-20250103.xsd#InventoryDetails"/>
  <link:calculationLink xlink:role="http://www.exelixis.com/role/InventoryDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryGross_9e5550ae-2781-4693-89cf-dd98e48a3d0c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InventoryGross"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryRawMaterials_bc6647ad-3c0a-44d1-9cc7-c992385a85f6" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InventoryRawMaterials"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_InventoryGross_9e5550ae-2781-4693-89cf-dd98e48a3d0c" xlink:to="loc_us-gaap_InventoryRawMaterials_bc6647ad-3c0a-44d1-9cc7-c992385a85f6" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryWorkInProcess_91d756ba-75c8-4ceb-a7fc-ab3689f4c8ce" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InventoryWorkInProcess"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_InventoryGross_9e5550ae-2781-4693-89cf-dd98e48a3d0c" xlink:to="loc_us-gaap_InventoryWorkInProcess_91d756ba-75c8-4ceb-a7fc-ab3689f4c8ce" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryFinishedGoods_ba44c2e7-e746-4893-83e4-5664d18f87bd" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InventoryFinishedGoods"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_InventoryGross_9e5550ae-2781-4693-89cf-dd98e48a3d0c" xlink:to="loc_us-gaap_InventoryFinishedGoods_ba44c2e7-e746-4893-83e4-5664d18f87bd" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.exelixis.com/role/PropertyandEquipmentScheduleofPropertyandEquipmentDetails" xlink:type="simple" xlink:href="exel-20250103.xsd#PropertyandEquipmentScheduleofPropertyandEquipmentDetails"/>
  <link:calculationLink xlink:role="http://www.exelixis.com/role/PropertyandEquipmentScheduleofPropertyandEquipmentDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentNet_f30c192c-5acf-491e-afe4-14952c268dc2" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PropertyPlantAndEquipmentNet"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentGross_d25af583-03d2-43c0-a59e-1025b6e55fc7" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PropertyPlantAndEquipmentGross"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentNet_f30c192c-5acf-491e-afe4-14952c268dc2" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentGross_d25af583-03d2-43c0-a59e-1025b6e55fc7" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment_341d2032-627c-4fd5-89f8-cae91f94581d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentNet_f30c192c-5acf-491e-afe4-14952c268dc2" xlink:to="loc_us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment_341d2032-627c-4fd5-89f8-cae91f94581d" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.exelixis.com/role/ProvisionForIncomeTaxesComponentsofIncomeTaxExpenseBenefitDetails" xlink:type="simple" xlink:href="exel-20250103.xsd#ProvisionForIncomeTaxesComponentsofIncomeTaxExpenseBenefitDetails"/>
  <link:calculationLink xlink:role="http://www.exelixis.com/role/ProvisionForIncomeTaxesComponentsofIncomeTaxExpenseBenefitDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CurrentIncomeTaxExpenseBenefit_9b56e0a3-2f64-46e1-ad21-9cbc41a9799e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CurrentIncomeTaxExpenseBenefit"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CurrentFederalTaxExpenseBenefit_14110d42-3e90-49a5-b684-15a0ef73cab3" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CurrentFederalTaxExpenseBenefit"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CurrentIncomeTaxExpenseBenefit_9b56e0a3-2f64-46e1-ad21-9cbc41a9799e" xlink:to="loc_us-gaap_CurrentFederalTaxExpenseBenefit_14110d42-3e90-49a5-b684-15a0ef73cab3" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CurrentStateAndLocalTaxExpenseBenefit_fce43433-d107-4090-9c32-3f09fbb4f6a8" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CurrentStateAndLocalTaxExpenseBenefit"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CurrentIncomeTaxExpenseBenefit_9b56e0a3-2f64-46e1-ad21-9cbc41a9799e" xlink:to="loc_us-gaap_CurrentStateAndLocalTaxExpenseBenefit_fce43433-d107-4090-9c32-3f09fbb4f6a8" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxExpenseBenefit_f179f1d4-fb38-4e3c-bd90-9da0ebaa75b8" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeTaxExpenseBenefit"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CurrentIncomeTaxExpenseBenefit_8e58a3e1-35ea-4f8a-8303-e590bb2aaabf" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CurrentIncomeTaxExpenseBenefit"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_IncomeTaxExpenseBenefit_f179f1d4-fb38-4e3c-bd90-9da0ebaa75b8" xlink:to="loc_us-gaap_CurrentIncomeTaxExpenseBenefit_8e58a3e1-35ea-4f8a-8303-e590bb2aaabf" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredIncomeTaxExpenseBenefit_ed41a303-4712-47fd-bff1-4e334405fb19" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DeferredIncomeTaxExpenseBenefit"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_IncomeTaxExpenseBenefit_f179f1d4-fb38-4e3c-bd90-9da0ebaa75b8" xlink:to="loc_us-gaap_DeferredIncomeTaxExpenseBenefit_ed41a303-4712-47fd-bff1-4e334405fb19" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredIncomeTaxExpenseBenefit_c4341eef-fa72-4cea-8753-5d9674a48fe0" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DeferredIncomeTaxExpenseBenefit"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredFederalIncomeTaxExpenseBenefit_3e8da944-7ba0-404a-ad86-61ad0d171d3f" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DeferredFederalIncomeTaxExpenseBenefit"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_DeferredIncomeTaxExpenseBenefit_c4341eef-fa72-4cea-8753-5d9674a48fe0" xlink:to="loc_us-gaap_DeferredFederalIncomeTaxExpenseBenefit_3e8da944-7ba0-404a-ad86-61ad0d171d3f" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredStateAndLocalIncomeTaxExpenseBenefit_3423248b-25eb-4c0d-8195-45dca3bbf379" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DeferredStateAndLocalIncomeTaxExpenseBenefit"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_DeferredIncomeTaxExpenseBenefit_c4341eef-fa72-4cea-8753-5d9674a48fe0" xlink:to="loc_us-gaap_DeferredStateAndLocalIncomeTaxExpenseBenefit_3423248b-25eb-4c0d-8195-45dca3bbf379" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.exelixis.com/role/ProvisionForIncomeTaxesScheduleofReconciliationofIncomeTaxesattheStatutoryFederalIncomeTaxRatetoNetIncomeTaxesDetails" xlink:type="simple" xlink:href="exel-20250103.xsd#ProvisionForIncomeTaxesScheduleofReconciliationofIncomeTaxesattheStatutoryFederalIncomeTaxRatetoNetIncomeTaxesDetails"/>
  <link:calculationLink xlink:role="http://www.exelixis.com/role/ProvisionForIncomeTaxesScheduleofReconciliationofIncomeTaxesattheStatutoryFederalIncomeTaxRatetoNetIncomeTaxesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxExpenseBenefit_1c97bd4f-19eb-4e29-a1a6-43cc6d997bef" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeTaxExpenseBenefit"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxReconciliationIncomeTaxExpenseBenefitAtFederalStatutoryIncomeTaxRate_9955fa9d-5776-42d1-89bd-285864226b7a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeTaxReconciliationIncomeTaxExpenseBenefitAtFederalStatutoryIncomeTaxRate"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_IncomeTaxExpenseBenefit_1c97bd4f-19eb-4e29-a1a6-43cc6d997bef" xlink:to="loc_us-gaap_IncomeTaxReconciliationIncomeTaxExpenseBenefitAtFederalStatutoryIncomeTaxRate_9955fa9d-5776-42d1-89bd-285864226b7a" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxReconciliationStateAndLocalIncomeTaxes_80cfc39a-dbb6-4918-be26-6539467d1775" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeTaxReconciliationStateAndLocalIncomeTaxes"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_IncomeTaxExpenseBenefit_1c97bd4f-19eb-4e29-a1a6-43cc6d997bef" xlink:to="loc_us-gaap_IncomeTaxReconciliationStateAndLocalIncomeTaxes_80cfc39a-dbb6-4918-be26-6539467d1775" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxReconciliationChangeInDeferredTaxAssetsValuationAllowance_d5a9bff5-18a2-4cbd-8485-0f6840a5e637" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeTaxReconciliationChangeInDeferredTaxAssetsValuationAllowance"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_IncomeTaxExpenseBenefit_1c97bd4f-19eb-4e29-a1a6-43cc6d997bef" xlink:to="loc_us-gaap_IncomeTaxReconciliationChangeInDeferredTaxAssetsValuationAllowance_d5a9bff5-18a2-4cbd-8485-0f6840a5e637" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxReconciliationTaxCreditsResearch_5e2e0a91-4d97-42bc-9a70-c28276a8b711" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeTaxReconciliationTaxCreditsResearch"/>
    <link:calculationArc order="4" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_IncomeTaxExpenseBenefit_1c97bd4f-19eb-4e29-a1a6-43cc6d997bef" xlink:to="loc_us-gaap_IncomeTaxReconciliationTaxCreditsResearch_5e2e0a91-4d97-42bc-9a70-c28276a8b711" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxReconciliationNondeductibleExpenseShareBasedCompensationCost_93dbda4b-6162-4638-9471-aaa6c4eef745" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeTaxReconciliationNondeductibleExpenseShareBasedCompensationCost"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_IncomeTaxExpenseBenefit_1c97bd4f-19eb-4e29-a1a6-43cc6d997bef" xlink:to="loc_us-gaap_IncomeTaxReconciliationNondeductibleExpenseShareBasedCompensationCost_93dbda4b-6162-4638-9471-aaa6c4eef745" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_exel_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseDeferredCompensation_e71d2bbb-dc28-4ba8-8f11-c707000cd7df" xlink:href="exel-20250103.xsd#exel_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseDeferredCompensation"/>
    <link:calculationArc order="6" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_IncomeTaxExpenseBenefit_1c97bd4f-19eb-4e29-a1a6-43cc6d997bef" xlink:to="loc_exel_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseDeferredCompensation_e71d2bbb-dc28-4ba8-8f11-c707000cd7df" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxReconciliationOtherAdjustments_2c2e74ce-ef20-4c43-b66a-6ccda9c228b1" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeTaxReconciliationOtherAdjustments"/>
    <link:calculationArc order="7" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_IncomeTaxExpenseBenefit_1c97bd4f-19eb-4e29-a1a6-43cc6d997bef" xlink:to="loc_us-gaap_IncomeTaxReconciliationOtherAdjustments_2c2e74ce-ef20-4c43-b66a-6ccda9c228b1" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_exel_EffectiveIncomeTaxRateReconciliationBrandedPrescriptionDrugFee_502e0d88-7f53-4018-bf97-41bf80bdf419" xlink:href="exel-20250103.xsd#exel_EffectiveIncomeTaxRateReconciliationBrandedPrescriptionDrugFee"/>
    <link:calculationArc order="8" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_IncomeTaxExpenseBenefit_1c97bd4f-19eb-4e29-a1a6-43cc6d997bef" xlink:to="loc_exel_EffectiveIncomeTaxRateReconciliationBrandedPrescriptionDrugFee_502e0d88-7f53-4018-bf97-41bf80bdf419" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_exel_EffectiveIncomeTaxRateReconciliationNondeductibleWarrantPurchase_e60083b6-c2e4-45ac-8379-6f6d9304d0d1" xlink:href="exel-20250103.xsd#exel_EffectiveIncomeTaxRateReconciliationNondeductibleWarrantPurchase"/>
    <link:calculationArc order="9" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_IncomeTaxExpenseBenefit_1c97bd4f-19eb-4e29-a1a6-43cc6d997bef" xlink:to="loc_exel_EffectiveIncomeTaxRateReconciliationNondeductibleWarrantPurchase_e60083b6-c2e4-45ac-8379-6f6d9304d0d1" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.exelixis.com/role/ProvisionForIncomeTaxesScheduleofDeferredAssetsandLiabilitiesDetails" xlink:type="simple" xlink:href="exel-20250103.xsd#ProvisionForIncomeTaxesScheduleofDeferredAssetsandLiabilitiesDetails"/>
  <link:calculationLink xlink:role="http://www.exelixis.com/role/ProvisionForIncomeTaxesScheduleofDeferredAssetsandLiabilitiesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredTaxAssetsGross_82b6a9a1-b085-44d9-974a-ffcb60aca6b0" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DeferredTaxAssetsGross"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredTaxAssetsOperatingLossCarryforwards_df39ca8b-6de7-45b2-add8-831b0d9aa86e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DeferredTaxAssetsOperatingLossCarryforwards"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_DeferredTaxAssetsGross_82b6a9a1-b085-44d9-974a-ffcb60aca6b0" xlink:to="loc_us-gaap_DeferredTaxAssetsOperatingLossCarryforwards_df39ca8b-6de7-45b2-add8-831b0d9aa86e" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredTaxAssetsTaxCreditCarryforwards_dc6729f1-f235-4c7a-abeb-90f20f30b559" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DeferredTaxAssetsTaxCreditCarryforwards"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_DeferredTaxAssetsGross_82b6a9a1-b085-44d9-974a-ffcb60aca6b0" xlink:to="loc_us-gaap_DeferredTaxAssetsTaxCreditCarryforwards_dc6729f1-f235-4c7a-abeb-90f20f30b559" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredTaxAssetsPropertyPlantAndEquipment_277049d2-fcbd-436e-85e2-25a1d946a6ce" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DeferredTaxAssetsPropertyPlantAndEquipment"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_DeferredTaxAssetsGross_82b6a9a1-b085-44d9-974a-ffcb60aca6b0" xlink:to="loc_us-gaap_DeferredTaxAssetsPropertyPlantAndEquipment_277049d2-fcbd-436e-85e2-25a1d946a6ce" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_exel_DeferredTaxAssetsLeaseLiabilities_4eea49a7-d81d-47cf-9fcd-0e98fc6fdb39" xlink:href="exel-20250103.xsd#exel_DeferredTaxAssetsLeaseLiabilities"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_DeferredTaxAssetsGross_82b6a9a1-b085-44d9-974a-ffcb60aca6b0" xlink:to="loc_exel_DeferredTaxAssetsLeaseLiabilities_4eea49a7-d81d-47cf-9fcd-0e98fc6fdb39" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredTaxAssetsTaxDeferredExpenseReservesAndAccrualsReserves_93d358db-b12b-4cd3-b0f2-29b87121b071" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DeferredTaxAssetsTaxDeferredExpenseReservesAndAccrualsReserves"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_DeferredTaxAssetsGross_82b6a9a1-b085-44d9-974a-ffcb60aca6b0" xlink:to="loc_us-gaap_DeferredTaxAssetsTaxDeferredExpenseReservesAndAccrualsReserves_93d358db-b12b-4cd3-b0f2-29b87121b071" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredTaxAssetsOther_3e550098-6269-45a7-bce6-9a96f5226675" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DeferredTaxAssetsOther"/>
    <link:calculationArc order="6" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_DeferredTaxAssetsGross_82b6a9a1-b085-44d9-974a-ffcb60aca6b0" xlink:to="loc_us-gaap_DeferredTaxAssetsOther_3e550098-6269-45a7-bce6-9a96f5226675" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredTaxAssetsTaxDeferredExpenseCompensationAndBenefitsShareBasedCompensationCost_5a367538-49f4-47e8-98a2-280815f57db7" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DeferredTaxAssetsTaxDeferredExpenseCompensationAndBenefitsShareBasedCompensationCost"/>
    <link:calculationArc order="7" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_DeferredTaxAssetsGross_82b6a9a1-b085-44d9-974a-ffcb60aca6b0" xlink:to="loc_us-gaap_DeferredTaxAssetsTaxDeferredExpenseCompensationAndBenefitsShareBasedCompensationCost_5a367538-49f4-47e8-98a2-280815f57db7" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredTaxAssetsLiabilitiesNet_e128bf2c-e2d9-4364-a2c3-61bc515d7728" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DeferredTaxAssetsLiabilitiesNet"/>
    <link:loc xlink:type="locator" xlink:label="loc_exel_DeferredTaxLiabilitiesLeaseRightOfUseAssets_4058983e-cf31-416a-a5d3-2b8228f36be9" xlink:href="exel-20250103.xsd#exel_DeferredTaxLiabilitiesLeaseRightOfUseAssets"/>
    <link:calculationArc order="1" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_DeferredTaxAssetsLiabilitiesNet_e128bf2c-e2d9-4364-a2c3-61bc515d7728" xlink:to="loc_exel_DeferredTaxLiabilitiesLeaseRightOfUseAssets_4058983e-cf31-416a-a5d3-2b8228f36be9" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredTaxAssetsNet_564d5e60-5137-4fe7-b19b-5fec5d734d0a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DeferredTaxAssetsNet"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_DeferredTaxAssetsLiabilitiesNet_e128bf2c-e2d9-4364-a2c3-61bc515d7728" xlink:to="loc_us-gaap_DeferredTaxAssetsNet_564d5e60-5137-4fe7-b19b-5fec5d734d0a" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredTaxAssetsNet_4c9d2f6c-1c53-4385-a853-32f65f428f31" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DeferredTaxAssetsNet"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredTaxAssetsGross_31831134-c51e-4079-8c59-a539854f04af" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DeferredTaxAssetsGross"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_DeferredTaxAssetsNet_4c9d2f6c-1c53-4385-a853-32f65f428f31" xlink:to="loc_us-gaap_DeferredTaxAssetsGross_31831134-c51e-4079-8c59-a539854f04af" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredTaxAssetsValuationAllowance_3a2e2ec5-1476-4a06-80d1-0c559cc925cb" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DeferredTaxAssetsValuationAllowance"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_DeferredTaxAssetsNet_4c9d2f6c-1c53-4385-a853-32f65f428f31" xlink:to="loc_us-gaap_DeferredTaxAssetsValuationAllowance_3a2e2ec5-1476-4a06-80d1-0c559cc925cb" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.exelixis.com/role/NetIncomePerShareComputationofBasicandDilutedNetIncomePerShareDetails" xlink:type="simple" xlink:href="exel-20250103.xsd#NetIncomePerShareComputationofBasicandDilutedNetIncomePerShareDetails"/>
  <link:calculationLink xlink:role="http://www.exelixis.com/role/NetIncomePerShareComputationofBasicandDilutedNetIncomePerShareDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_10dd8b87-0b90-4985-bf8e-5ec3ddd25fa6" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_028f757e-d360-4ad0-a280-066467bbb0a9" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_WeightedAverageNumberOfSharesOutstandingBasic"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_10dd8b87-0b90-4985-bf8e-5ec3ddd25fa6" xlink:to="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_028f757e-d360-4ad0-a280-066467bbb0a9" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WeightedAverageNumberDilutedSharesOutstandingAdjustment_d0aa44ed-81fc-44df-bc59-4e166884850f" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_WeightedAverageNumberDilutedSharesOutstandingAdjustment"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_10dd8b87-0b90-4985-bf8e-5ec3ddd25fa6" xlink:to="loc_us-gaap_WeightedAverageNumberDilutedSharesOutstandingAdjustment_d0aa44ed-81fc-44df-bc59-4e166884850f" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.exelixis.com/role/CommitmentsandContingenciesBalanceSheetClassificationofLeaseLiabilitiesDetails" xlink:type="simple" xlink:href="exel-20250103.xsd#CommitmentsandContingenciesBalanceSheetClassificationofLeaseLiabilitiesDetails"/>
  <link:calculationLink xlink:role="http://www.exelixis.com/role/CommitmentsandContingenciesBalanceSheetClassificationofLeaseLiabilitiesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseLiability_ed73a45e-26fd-4f32-aaeb-50057453a046" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingLeaseLiability"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseLiabilityCurrent_a1abb93d-257c-4521-831c-ed0f285fcff6" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingLeaseLiabilityCurrent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_OperatingLeaseLiability_ed73a45e-26fd-4f32-aaeb-50057453a046" xlink:to="loc_us-gaap_OperatingLeaseLiabilityCurrent_a1abb93d-257c-4521-831c-ed0f285fcff6" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseLiabilityNoncurrent_f0e4b68f-b9fd-4d79-b767-d5569f8b2e69" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingLeaseLiabilityNoncurrent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_OperatingLeaseLiability_ed73a45e-26fd-4f32-aaeb-50057453a046" xlink:to="loc_us-gaap_OperatingLeaseLiabilityNoncurrent_f0e4b68f-b9fd-4d79-b767-d5569f8b2e69" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.exelixis.com/role/CommitmentsandContingenciesComponentsofLeaseExpenseDetails" xlink:type="simple" xlink:href="exel-20250103.xsd#CommitmentsandContingenciesComponentsofLeaseExpenseDetails"/>
  <link:calculationLink xlink:role="http://www.exelixis.com/role/CommitmentsandContingenciesComponentsofLeaseExpenseDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LeaseCost_9e8d6695-a60c-4851-afc6-f00d88547b3b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LeaseCost"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseCost_342076c0-4d9a-449b-8a34-b2fe83d7fa09" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingLeaseCost"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LeaseCost_9e8d6695-a60c-4851-afc6-f00d88547b3b" xlink:to="loc_us-gaap_OperatingLeaseCost_342076c0-4d9a-449b-8a34-b2fe83d7fa09" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_VariableLeaseCost_e92de569-cdb5-42e5-8028-a16ec85c646f" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_VariableLeaseCost"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LeaseCost_9e8d6695-a60c-4851-afc6-f00d88547b3b" xlink:to="loc_us-gaap_VariableLeaseCost_e92de569-cdb5-42e5-8028-a16ec85c646f" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.exelixis.com/role/CommitmentsandContingenciesMaturitiesofOperatingLeaseLiabilitiesDetails" xlink:type="simple" xlink:href="exel-20250103.xsd#CommitmentsandContingenciesMaturitiesofOperatingLeaseLiabilitiesDetails"/>
  <link:calculationLink xlink:role="http://www.exelixis.com/role/CommitmentsandContingenciesMaturitiesofOperatingLeaseLiabilitiesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_a86736b0-2d82-4f13-b8ca-1bdb0566eab5" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount_ed7b1923-0e5a-43b4-9262-bad241bf5eb2" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_a86736b0-2d82-4f13-b8ca-1bdb0566eab5" xlink:to="loc_us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount_ed7b1923-0e5a-43b4-9262-bad241bf5eb2" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseLiability_6d9c1e4a-2fd8-4a3b-b23a-d2bd0745e0c2" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingLeaseLiability"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_a86736b0-2d82-4f13-b8ca-1bdb0566eab5" xlink:to="loc_us-gaap_OperatingLeaseLiability_6d9c1e4a-2fd8-4a3b-b23a-d2bd0745e0c2" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.exelixis.com/role/CommitmentsandContingenciesMaturitiesofOperatingLeaseLiabilitiesDetails_1" xlink:type="simple" xlink:href="exel-20250103.xsd#CommitmentsandContingenciesMaturitiesofOperatingLeaseLiabilitiesDetails_1"/>
  <link:calculationLink xlink:role="http://www.exelixis.com/role/CommitmentsandContingenciesMaturitiesofOperatingLeaseLiabilitiesDetails_1" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_a5ddcb7b-6ec9-456d-9304-1c026803313f" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths_8b3a9367-2e2e-44bb-a5c6-eecbb89e26c1" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_a5ddcb7b-6ec9-456d-9304-1c026803313f" xlink:to="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths_8b3a9367-2e2e-44bb-a5c6-eecbb89e26c1" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo_d3f80932-2da9-4ce4-b6f7-93b8862c9456" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_a5ddcb7b-6ec9-456d-9304-1c026803313f" xlink:to="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo_d3f80932-2da9-4ce4-b6f7-93b8862c9456" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree_539f07df-6642-4845-9ba2-ff5b92695fa5" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_a5ddcb7b-6ec9-456d-9304-1c026803313f" xlink:to="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree_539f07df-6642-4845-9ba2-ff5b92695fa5" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour_a0071a48-9a3f-4a2d-a81f-8b3266d78e12" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_a5ddcb7b-6ec9-456d-9304-1c026803313f" xlink:to="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour_a0071a48-9a3f-4a2d-a81f-8b3266d78e12" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive_3b791d5e-f306-4e9c-b242-f6199673832d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_a5ddcb7b-6ec9-456d-9304-1c026803313f" xlink:to="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive_3b791d5e-f306-4e9c-b242-f6199673832d" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive_90a725b5-5977-4ae1-9ef0-df0cc6fde31d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive"/>
    <link:calculationArc order="6" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_a5ddcb7b-6ec9-456d-9304-1c026803313f" xlink:to="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive_90a725b5-5977-4ae1-9ef0-df0cc6fde31d" xlink:type="arc"/>
  </link:calculationLink>
</link:linkbase>
