| 9/2/2021 | Frostburg State | 20 | at | Kentucky Wesleyan (3-8) | 13 | | | at GMAC |
| 9/11/2021 | Frostburg State | 34 | at | West Virginia State (6-5,6-4) | 21 | | | |
| 9/16/2021 | Charleston WV (8-2,8-2) | 24 | at | Frostburg State | 30 | 2OT | | |
| 9/25/2021 | Frostburg State | 42 | at | Concord (4-6,4-6) | 23 | | | |
| 10/2/2021 | UNC Pembroke (5-5,5-4) | 21 | at | Frostburg State | 51 | | | |
| 10/9/2021 | Frostburg State | 21 | at | Notre Dame OH (11-2,9-1) | 23 | | | |
| 10/16/2021 | Wheeling (5-6,5-5) | 17 | at | Frostburg State | 41 | | | |
| 10/23/2021 | Frostburg State | 49 | at | Fairmont State (5-6,5-5) | 14 | | | |
| 10/30/2021 | Frostburg State | 45 | at | Alderson-Broaddus (1-10,1-9) | 7 | | | |
| 11/6/2021 | West Virginia Wesleyan (0-10,0-9) | 14 | at | Frostburg State | 55 | | | |
| 11/11/2021 | West Liberty (4-7,4-6) | 3 | at | Frostburg State | 56 | | | |