Schedule:
| Game | Date | Away Team (Rank) | Away Score | Home Team (Rank) | Home Score | Game Status | Result | Margin |
|---|---|---|---|---|---|---|---|---|
| 1 | 2021-09-04 | East Tennessee State | 23 | Vanderbilt | 3 | Final | W | 20 |
| 2 | 2021-09-11 | UVA-Wise | 14 | East Tennessee State | 45 | Final | W | 31 |
| 3 | 2021-09-18 | Delaware State | 6 | East Tennessee State | 38 | Final | W | 32 |
| 4 | 2021-09-25 | East Tennessee State | 55 | Samford | 48 | Final(OT) | W | 7 |
| 5 | 2021-10-02 | Wofford | 21 | East Tennessee State | 27 | Final | W | 6 |
| 6 | 2021-10-09 | The Citadel | 21 | East Tennessee State | 48 | Final | W | 27 |
| 7 | 2021-10-16 | East Tennessee State | 16 | Chattanooga | 21 | Final | L | -5 |
| 8 | 2021-10-23 | East Tennessee State | 17 | Furman | 13 | Final | W | 4 |
| 9 | 2021-11-06 | Virginia Military | 20 | East Tennessee State | 27 | Final | W | 7 |
| 10 | 2021-11-13 | East Tennessee State | 56 | Western Carolina | 35 | Final | W | 21 |
| 11 | 2021-11-20 | Mercer | 35 | East Tennessee State | 38 | Final | W | 3 |
| 12 | 2021-12-04 | Kennesaw State (123) | 31 | East Tennessee State (105) | 32 | Final | W | 1 |
| 13 | 2021-12-11 | East Tennessee State (105) | 3 | North Dakota State (86) | 27 | Final | L | -24 |