Schedule:
| Game | Date | Away Team (Rank) | Away Score | Home Team (Rank) | Home Score | Game Status | Result | Margin |
|---|---|---|---|---|---|---|---|---|
| 1 | 2021-09-04 | Missouri State | 16 | Oklahoma State | 23 | Final | L | -7 |
| 2 | 2021-09-11 | Central Arkansas | 34 | Missouri State | 43 | Final | W | 9 |
| 3 | 2021-09-25 | South Dakota | 23 | Missouri State | 31 | Final | W | 8 |
| 4 | 2021-10-02 | Missouri State | 41 | Illinois State | 20 | Final | W | 21 |
| 5 | 2021-10-09 | Missouri State | 33 | Youngstown State | 41 | Final | L | -8 |
| 6 | 2021-10-16 | Indiana State | 7 | Missouri State | 37 | Final | W | 30 |
| 7 | 2021-10-23 | Missouri State | 20 | North Dakota State | 27 | Final | L | -7 |
| 8 | 2021-10-30 | North Dakota | 28 | Missouri State | 32 | Final | W | 4 |
| 9 | 2021-11-06 | Missouri State | 38 | Southern Illinois | 28 | Final | W | 10 |
| 10 | 2021-11-13 | Northern Iowa | 27 | Missouri State | 34 | Final | W | 7 |
| 11 | 2021-11-20 | Missouri State | 55 | Dixie State | 24 | Final | W | 31 |
| 12 | 2021-11-27 | Tennessee-Martin (138) | 32 | Missouri State (132) | 31 | Final | L | -1 |