Schedule:
| Game | Date | Away Team (Rank) | Away Score | Home Team (Rank) | Home Score | Game Status | Result | Margin |
|---|---|---|---|---|---|---|---|---|
| 1 | 2021-09-02 | East Carolina | 19 | Appalachian State | 33 | Final | W | 14 |
| 2 | 2021-09-11 | Appalachian State | 23 | Miami | 25 | Final | L | -2 |
| 3 | 2021-09-18 | Elon | 10 | Appalachian State | 44 | Final | W | 34 |
| 4 | 2021-09-23 | Marshall | 30 | Appalachian State | 31 | Final | W | 1 |
| 5 | 2021-10-02 | Appalachian State | 45 | Georgia State | 16 | Final | W | 29 |
| 6 | 2021-10-12 | Appalachian State | 13 | Louisiana | 41 | Final | L | -28 |
| 7 | 2021-10-20 | Coastal Carolina | 27 | Appalachian State | 30 | Final | W | 3 |
| 8 | 2021-10-30 | Louisiana-Monroe | 28 | Appalachian State | 59 | Final | W | 31 |
| 9 | 2021-11-06 | Appalachian State | 48 | Arkansas State | 14 | Final | W | 34 |
| 10 | 2021-11-13 | South Alabama | 7 | Appalachian State | 31 | Final | W | 24 |
| 11 | 2021-11-20 | Appalachian State | 45 | Troy | 7 | Final | W | 38 |
| 12 | 2021-11-27 | Georgia Southern (133) | 3 | Appalachian State (24) | 27 | Final | W | 24 |
| 13 | 2021-12-04 | Appalachian State (28) | 16 | Louisiana (17) | 24 | Final | L | -8 |
| 14 | 2021-12-18 | Western Kentucky (42) | 59 | Appalachian State (36) | 38 | Final | L | -21 |