<?xml version="1.0" encoding="us-ascii"?>
<!--XBRL document created with Toppan Merrill Bridge  9.6.8119.21675 -->
<!--Based on XBRL 2.1-->
<!--Created on: 4/28/2022 6:37:48 PM-->
<!--Modified on: 4/28/2022 6:37:48 PM-->
<xsd:schema targetNamespace="http://www.southstatebank.com/20220428" attributeFormDefault="unqualified" elementFormDefault="qualified" xmlns:xsd="http://www.w3.org/2001/XMLSchema" xmlns:dei="http://xbrl.sec.gov/dei/2021" xmlns:us-gaap="http://fasb.org/us-gaap/2021-01-31" xmlns:srt-types="http://fasb.org/srt-types/2021-01-31" xmlns:us-roles="http://fasb.org/us-roles/2021-01-31" xmlns:ref="http://www.xbrl.org/2006/ref" xmlns:xbrldt="http://xbrl.org/2005/xbrldt" xmlns:currency="http://xbrl.sec.gov/currency/2021" xmlns:xl="http://www.xbrl.org/2003/XLink" xmlns:naics="http://xbrl.sec.gov/naics/2021" xmlns:srt-roles="http://fasb.org/srt-roles/2021-01-31" xmlns:country="http://xbrl.sec.gov/country/2021" xmlns:utr="http://www.xbrl.org/2009/utr" xmlns:srt="http://fasb.org/srt/2021-01-31" xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:exch="http://xbrl.sec.gov/exch/2021" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:sic="http://xbrl.sec.gov/sic/2021" xmlns:us-types="http://fasb.org/us-types/2021-01-31" xmlns:negated="http://www.xbrl.org/2009/role/negated" xmlns:stpr="http://xbrl.sec.gov/stpr/2021" xmlns:attributeFormDefault="unqualified" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:xbrli="http://www.xbrl.org/2003/instance" xmlns:dtr-types="http://www.xbrl.org/dtr/type/2020-01-21" xmlns:ssb="http://www.southstatebank.com/20220428" xmlns:enum2="http://xbrl.org/2020/extensible-enumerations-2.0" xmlns:deprecated="http://www.xbrl.org/2009/role/deprecated" xmlns:net="http://www.xbrl.org/2009/role/net">
  <xsd:annotation>
    <xsd:appinfo>
      <link:roleType roleURI="http://www.southstatebank.com/role/DocumentDocumentAndEntityInformation" id="DocumentDocumentAndEntityInformation">
        <link:definition>00090 - Document - Document and Entity Information</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:linkbaseRef xlink:type="simple" xlink:href="ssb-20220428_pre.xml" xlink:role="http://www.xbrl.org/2003/role/presentationLinkbaseRef" xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" />
      <link:linkbaseRef xlink:type="simple" xlink:href="ssb-20220428_lab.xml" xlink:role="http://www.xbrl.org/2003/role/labelLinkbaseRef" xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" />
    </xsd:appinfo>
  </xsd:annotation>
  <xsd:import namespace="http://www.xbrl.org/2003/instance" schemaLocation="http://www.xbrl.org/2003/xbrl-instance-2003-12-31.xsd" />
  <xsd:import namespace="http://xbrl.org/2005/xbrldt" schemaLocation="http://www.xbrl.org/2005/xbrldt-2005.xsd" />
  <xsd:import namespace="http://xbrl.sec.gov/dei/2021" schemaLocation="https://xbrl.sec.gov/dei/2021/dei-2021.xsd" />
</xsd:schema>
