Schedule:
| Game | Date | Away Team (Rank) | Away Score | Home Team (Rank) | Home Score | Game Status | Result | Margin |
|---|---|---|---|---|---|---|---|---|
| 1 | 2022-09-03 | Southeast Missouri State (190) | 10 | Iowa State (34) | 42 | Final | L | -32 |
| 2 | 2022-09-10 | Southeast Missouri State (190) | 34 | Southern Illinois (137) | 31 | Final | W | 3 |
| 3 | 2022-09-17 | Nicholls State (223) | 16 | Southeast Missouri State (143) | 42 | Final | W | 26 |
| 4 | 2022-09-24 | Central Arkansas (228) | 27 | Southeast Missouri State (147) | 35 | Final | W | 8 |
| 5 | 2022-10-01 | Southeast Missouri State (136) | 49 | Lindenwood (200) | 28 | Final | W | 21 |
| 6 | 2022-10-08 | Tennessee Tech (205) | 20 | Southeast Missouri State (131) | 34 | Final | W | 14 |
| 7 | 2022-10-22 | Southeast Missouri State (135) | 51 | Northwestern State (238) | 16 | Final | W | 35 |
| 8 | 2022-10-29 | Eastern Kentucky (158) | 28 | Southeast Missouri State (146) | 23 | Final | L | -5 |
| 9 | 2022-11-05 | Southeast Missouri State (146) | 42 | Tennessee State (232) | 0 | Final | W | 42 |
| 10 | 2022-11-12 | Southeast Missouri State (146) | 31 | Eastern Illinois (238) | 7 | Final | W | 24 |
| 11 | 2022-11-19 | Murray State (244) | 22 | Southeast Missouri State (141) | 52 | Final | W | 30 |
| 12 | 2022-11-26 | Southeast Missouri State (156) | 24 | Montana (140) | 34 | Final | L | -10 |