American college football season
The 2021 Southeast Missouri State Redhawks football team represented Southeast Missouri State University as a member of the Ohio Valley Conference (OVC) during the 2021 NCAA Division I FCS football season. Led by eighth-year head coach Tom Matukewicz, the Redhawks compiled an overall record of 4–7 with a mark of 4–2 in conference play, tying for second place in the OVC. Southeast Missouri State played home games at Houck Stadium in Cape Girardeau, Missouri.
Schedule
Date | Time | Opponent | Site | TV | Result | Attendance |
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| 7:30 p.m. | No. 7 Southern Illinois* | | ESPN+ | L 21–47 | 4,075 |
September 11 | 7:00 p.m. | at No. 1 Sam Houston* | | ESPN+ | L 14–52 | 7,728 |
September 18 | 12:00 p.m. | at Missouri* | | ESPN+/SECN+ | L 28–59 | 46,598 |
September 25 | 3:00 p.m. | Tennessee State | - Houck Field
- Cape Girardeau, MO
| ESPN+ | W 47–14 | 3,896 |
October 2 | 2:30 p.m. | at Tennessee Tech | | ESPN+ | L 17–28 | 3,655 |
October 9 | 4:00 p.m. | at Austin Peay | | ESPN+ | W 30–14 | 6,729 |
October 16 | 3:00 p.m. | Murray State* | - Houck Field
- Cape Girardeau, MO
| ESPN+ | L 31–32 | 3,682 |
October 23 | 3:00 p.m. | at No. 13 UT Martin* | | ESPN+ | L 30–38 | 2,230 |
October 30 | 2:00 p.m. | Eastern Illinois | - Houck Field
- Cape Girardeau, MO
| ESPN+ | W 38–15 | 3,773 |
November 13 | 2:00 p.m. | at Murray State | | ESPN+ | L 10–28 | 6,313 |
November 20 | 2:00 p.m. | No. 13 UT Martin | - Houck Field
- Cape Girardeau, MO
| ESPN+ | W 31-14 | 3,219 |
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