The 2021 Midwestern State Mustangs football team represented Midwestern State University in the 2021 NCAA Division II football season.

They were led by head coach Bill Maskill, who was in his 20th season at Midwestern State.

The Mustangs played their home games at Memorial Stadium and were members of the Lone Star Conference.

On August 12, 2020, the Lone Star Conference postponed fall competition in 2020 for several sports due to the COVID-19 pandemic.

[4] Midwestern State announced their 2021 football schedule on March 24, 2021.