Schedule:
| Game | Date | Away Team (Rank) | Away Score | Home Team (Rank) | Home Score | Game Status | Result | Margin |
|---|---|---|---|---|---|---|---|---|
| 1 | 2021-09-02 | Tennessee Tech | 14 | Samford | 52 | Final | W | 38 |
| 2 | 2021-09-11 | Samford | 27 | Tennessee-Martin | 33 | Final | L | -6 |
| 3 | 2021-09-18 | Samford | 42 | Western Carolina | 37 | Final | W | 5 |
| 4 | 2021-09-25 | East Tennessee State | 55 | Samford | 48 | Final(OT) | L | -7 |
| 5 | 2021-10-02 | Samford | 42 | Mercer | 45 | Final | L | -3 |
| 6 | 2021-10-16 | Samford | 27 | Wofford | 24 | Final | W | 3 |
| 7 | 2021-10-23 | Chattanooga | 55 | Samford | 13 | Final | L | -42 |
| 8 | 2021-10-30 | Samford | 45 | Virginia Military | 46 | Final | L | -1 |
| 9 | 2021-11-06 | The Citadel | 14 | Samford | 35 | Final | W | 21 |
| 10 | 2021-11-13 | Samford | 52 | Florida | 70 | Final | L | -18 |
| 11 | 2021-11-20 | Furman | 41 | Samford | 34 | Final | L | -7 |