The 1921 College Football All-Southern Team consists of American football players selected to the College Football All-Southern Teams selected by various organizations for the 1921 Southern Intercollegiate Athletic Association football season. This was the last year before many schools left the Southern Intercollegiate Athletic Association (SIAA) for the Southern Conference (SoCon).
Centre posted the SIAA's best record and upset Harvard 6–0. Georgia Tech was also undefeated in conference play, as were Georgia and Vanderbilt, the latter two posting one tie against the other. Vanderbilt was the only one to remain undefeated overall, and were selected as a national champion retroactively by selector Clyde Berryman.