The 2021 Mississippi Valley State Delta Devils football team represented Mississippi Valley State University as a member of the East Division of the Southwestern Athletic Conference (SWAC) during the 2021 NCAA Division I FCS football season.

Led by fourth-year head coach Vincent Dancy, the Delta Devils compiled an overall record of 4–7 and a mark of 3–5 in conference play, tying for fourth place in the SWAC's East Division.

Mississippi Valley State played home games at Rice–Totten Stadium in Itta Bena, Mississippi.

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