The 2018–19 SFA South Region Challenge Cup was the 12th edition of the annual cup competition for senior non-league clubs in the central and southern regions of Scotland. This season saw the competition increase to 69 teams from the 42 who took part in 2017–18, thanks to the addition of 26 clubs to the East of Scotland Football League and the return of Wigtown and Bladnoch. The defending champions were Civil Service Strollers, who beat BSC Glasgow 2-1 after extra time in the final on 20 May 2018. However they were eliminated in the fourth round by Newtongrange Star.