The 2021 Eastern Illinois Panthers football team represented Eastern Illinois University as a member of the Ohio Valley Conference (OVC) during the 2021 NCAA Division I FCS football season.

Led by Adam Cushing in his third and final season as head coach, the Panthers compiled an overall record of 1–10 with a mark of 1–5 in conference play, tying for sixth place in the OVC.

The team played home games at O'Brien Field in Charleston, Illinois.

[1] The Panthers had two players selected to the preseason all-OVC team.

[2] Defense Jason Johnson – LB Special teams Matt Judd – KR