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

<!--XBRL Document Created with the Workiva Platform-->
<!--Copyright 2026 Workiva-->
<!--r:019c7d06-3109-7dec-9647-265602f5b795,g:04af5530-51d0-490d-b6f6-5d64281d7e01-->
<xs:schema xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:exel="http://www.exelixis.com/20260415" attributeFormDefault="unqualified" elementFormDefault="qualified" targetNamespace="http://www.exelixis.com/20260415">
  <xs:import namespace="http://www.xbrl.org/2003/linkbase" schemaLocation="http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd"/>
  <xs:import namespace="http://xbrl.sec.gov/dei-sub/2025" schemaLocation="https://xbrl.sec.gov/dei/2025/dei-sub-2025.xsd"/>
  <xs:import namespace="http://xbrl.sec.gov/ecd-sub/2025" schemaLocation="https://xbrl.sec.gov/ecd/2025/ecd-sub-2025.xsd"/>
  <xs:annotation>
    <xs:appinfo/>
  </xs:annotation>
</xs:schema>
