The 2021 SMU Mustangs football team represented Southern Methodist University during the 2021 NCAA Division I FBS football season.

The Mustangs played their home games at Gerald J. Ford Stadium in University Park, Texas, a separate city within the city limits of Dallas, competed as members of the American Athletic Conference (AAC).

The Mustangs were led by fourth-year coach Sonny Dykes—on November 29, it was announced that Dykes would leave the program to become the head coach at TCU.

After finishing their regular season with an 8–4 record, the Mustangs accepted a bid to play in the Fenway Bowl, where they were due to face the Virginia Cavaliers.

On December 26, the Cavaliers withdrew from the game, due to COVID-19 issues; the bowl was subsequently canceled.