| 9/2/2021 | Wheeling | 14 | at | Seton Hill (5-6) | 16 | | | at PSAC |
| 9/9/2021 | Notre Dame OH (11-2,9-1) | 31 | at | Wheeling | 15 | | | |
| 9/18/2021 | Alderson-Broaddus (1-10,1-9) | 6 | at | Wheeling | 28 | | | |
| 9/25/2021 | Wheeling | 27 | at | Glenville State (3-7,3-7) | 10 | | | |
| 10/2/2021 | West Virginia Wesleyan (0-10,0-9) | 0 | at | Wheeling | 38 | | | |
| 10/9/2021 | Wheeling | 28 | at | UNC Pembroke (5-5,5-4) | 34 | | | |
| 10/16/2021 | Wheeling | 17 | at | Frostburg State (10-1,9-1) | 41 | | | |
| 10/23/2021 | West Liberty (4-7,4-6) | 20 | at | Wheeling | 26 | OT | | |
| 10/30/2021 | Concord (4-6,4-6) | 14 | at | Wheeling | 15 | | | |
| 11/6/2021 | Wheeling | 20 | at | Charleston WV (8-2,8-2) | 38 | | | |
| 11/12/2021 | Wheeling | 14 | at | Fairmont State (5-6,5-5) | 29 | | | |