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 | L | -5 |
| 2 | 2021-09-04 | Eastern Illinois | 0 | South Carolina | 46 | Final | L | -46 |
| 3 | 2021-09-11 | Eastern Illinois | 10 | Dayton | 17 | Final | L | -7 |
| 4 | 2021-09-18 | Illinois State | 31 | Eastern Illinois | 24 | Final | L | -7 |
| 5 | 2021-09-25 | Eastern Illinois | 28 | Tennessee Tech | 14 | Final | W | 14 |
| 6 | 2021-10-02 | Eastern Illinois | 6 | Murray State | 22 | Final | L | -16 |
| 7 | 2021-10-16 | Tennessee-Martin | 28 | Eastern Illinois | 17 | Final | L | -11 |
| 8 | 2021-10-23 | Tennessee State | 28 | Eastern Illinois | 0 | Final | L | -28 |
| 9 | 2021-10-30 | Eastern Illinois | 15 | Southeast Missouri State | 38 | Final | L | -23 |
| 10 | 2021-11-06 | Eastern Illinois | 26 | Austin Peay | 42 | Final | L | -16 |
| 11 | 2021-11-20 | Murray State | 20 | Eastern Illinois | 13 | Final | L | -7 |