The 2020–21 SFA South Region Challenge Cup (known as The SoccerShop Challenge Cup for sponsorship reasons) was the 14th edition of the annual knockout cup competition for senior non-league clubs in the central and southern regions of Scotland. This season sees the tournament increase from 70 to 121 teams thanks to additional clubs joining the East of Scotland Football League and the inclusion of 67 clubs from the inaugural West of Scotland Football League. Due to Scottish Government restrictions, games were played behind closed doors because of the COVID-19 pandemic.