Schedule:
| Game | Date | Away Team (Rank) | Away Score | Home Team (Rank) | Home Score | Game Status | Result | Margin |
|---|---|---|---|---|---|---|---|---|
| 1 | 2021-09-04 | Eastern Kentucky | 31 | Western Carolina | 28 | Final | W | 3 |
| 2 | 2021-09-11 | Eastern Kentucky | 3 | Louisville | 30 | Final | L | -27 |
| 3 | 2021-09-18 | Indiana State | 23 | Eastern Kentucky | 21 | Final | L | -2 |
| 4 | 2021-09-25 | Austin Peay | 27 | Eastern Kentucky | 35 | Final | W | 8 |
| 5 | 2021-10-02 | Tarleton State | 3 | Eastern Kentucky | 20 | Final | W | 17 |
| 6 | 2021-10-09 | Abilene Christian | 15 | Eastern Kentucky | 30 | Final | W | 15 |
| 7 | 2021-10-16 | Eastern Kentucky | 38 | Central Arkansas | 35 | Final | W | 3 |
| 8 | 2021-10-30 | Lamar | 10 | Eastern Kentucky | 42 | Final | W | 32 |
| 9 | 2021-11-06 | Eastern Kentucky | 17 | Stephen F. Austin | 31 | Final | L | -14 |
| 10 | 2021-11-13 | Eastern Kentucky | 28 | Sam Houston State | 42 | Final | L | -14 |
| 11 | 2021-11-20 | Jacksonville State | 31 | Eastern Kentucky | 39 | Final(OT) | W | 8 |