Schedule:
| Game | Date | Away Team (Rank) | Away Score | Home Team (Rank) | Home Score | Game Status | Result | Margin |
|---|---|---|---|---|---|---|---|---|
| 1 | 2021-08-28 | Eastern Illinois | 21 | Indiana State | 26 | Final | W | 5 |
| 2 | 2021-09-11 | Indiana State | 6 | Northwestern | 24 | Final | L | -18 |
| 3 | 2021-09-18 | Indiana State | 23 | Eastern Kentucky | 21 | Final | W | 2 |
| 4 | 2021-09-25 | South Dakota State | 44 | Indiana State | 0 | Final | L | -44 |
| 5 | 2021-10-02 | Indiana State | 10 | South Dakota | 38 | Final | L | -28 |
| 6 | 2021-10-09 | Western Illinois | 27 | Indiana State | 37 | Final | W | 10 |
| 7 | 2021-10-16 | Indiana State | 7 | Missouri State | 37 | Final | L | -30 |
| 8 | 2021-10-23 | Youngstown State | 17 | Indiana State | 28 | Final | W | 11 |
| 9 | 2021-10-30 | Indiana State | 2 | North Dakota State | 44 | Final | L | -42 |
| 10 | 2021-11-13 | Southern Illinois | 47 | Indiana State | 21 | Final | L | -26 |
| 11 | 2021-11-20 | Indiana State | 15 | Illinois State | 10 | Final | W | 5 |