Schedule:
| Game | Date | Away Team (Rank) | Away Score | Home Team (Rank) | Home Score | Game Status | Result | Margin |
|---|---|---|---|---|---|---|---|---|
| 1 | 2021-09-04 | Butler | 7 | Illinois State | 49 | Final | W | 42 |
| 2 | 2021-09-11 | Illinois State | 0 | Western Michigan | 28 | Final | L | -28 |
| 3 | 2021-09-18 | Illinois State | 31 | Eastern Illinois | 24 | Final | W | 7 |
| 4 | 2021-09-25 | Illinois State | 17 | Southern Illinois | 35 | Final | L | -18 |
| 5 | 2021-10-02 | Missouri State | 41 | Illinois State | 20 | Final | L | -21 |
| 6 | 2021-10-16 | North Dakota State | 20 | Illinois State | 0 | Final | L | -20 |
| 7 | 2021-10-23 | Illinois State | 20 | South Dakota | 14 | Final | W | 6 |
| 8 | 2021-10-30 | Illinois State | 31 | Western Illinois | 38 | Final | L | -7 |
| 9 | 2021-11-06 | Northern Iowa | 10 | Illinois State | 17 | Final(OT) | W | 7 |
| 10 | 2021-11-13 | Illinois State | 7 | North Dakota | 14 | Final | L | -7 |
| 11 | 2021-11-20 | Indiana State | 15 | Illinois State | 10 | Final | L | -5 |