The 2021 Iowa State Cyclones football team represented Iowa State University as a member of Big 12 Conference during the 2021 NCAA Division I FBS football season. Led by sixth-year head coach Matt Campbell, the Cyclones compiled an overall record of 7–6 with a mark of 5–4 in conference play, placing fourth in the Big 12. Iowa State was invited to the Cheez-It Bowl, the Cyclones lost to Clemson. The team played home games at Jack Trice Stadium in Ames, Iowa.