| 9/4/2021 | Newberry | 31 | at | Barton | 7 | SAC | ||
| Lawrence Tech | 21 | at | Bluefield St WV | 14 | MSFA (NAIA) | |||
| Erskine | 27 | at | Catawba | 37 | @ SAC | |||
| 9/5/2021 | Emory & Henry | 36 | at | North Carolina Wesleyan | 7 | @ USASC (D3) | ||
| 9/11/2021 | Bluefield St WV | 35 | at | Elizabeth City State | 27 | @ CIAA | ||
| Bluefield | 46 | at | Emory & Henry | 45 | MSC (NAIA) | |||
| Barton | 38 | at | Erskine | 25 | ||||
| 9/18/2021 | Barton | 10 | at | Catawba | 17 | @ SAC | ||
| Erskine | 19 | at | Chowan | 49 | @ CIAA | |||
| Apprentice | 7 | at | Emory & Henry | 63 | None (Unk?) | |||
| Bluefield St WV | 20 | at | Johnson C Smith | 12 | @ CIAA | |||
| 9/25/2021 | Bridgewater VA | 17 | at | Emory & Henry | 38 | ODC (D3) | ||
| North Greenville | 38 | at | Erskine | 7 | GSC | |||
| Barton | 45 | at | Limestone | 7 | @ SAC | |||
| 10/2/2021 | Carson-Newman | 17 | at | Barton | 31 | SAC | ||
| Virginia U-Lynchburg | 13 | at | Erskine | 59 | None (Unk?) | |||
| 10/9/2021 | Fort Lauderdale | 9 | at | Bluefield St WV | 23 | None (Unk?) | ||
| Barton | 32 | at | Mars Hill | 40 | @ SAC | |||
| Emory & Henry | 31 | at | Randolph-Macon | 34 | @ ODC (D3) | |||
| Erskine | 6 | at | Savannah State | 39 | @ SIAC | |||
| 10/16/2021 | Wingate | 20 | at | Barton | 26 | OT | SAC | |
| Hampden-Sydney | 13 | at | Emory & Henry | 37 | ODC (D3) | |||
| Bluefield St WV | 19 | at | Erskine | 24 | ||||
| 10/23/2021 | Allen | 40 | at | Erskine | 47 | SIAC | ||
| Emory & Henry | 7 | at | Shenandoah | 9 | @ ODC (D3) | |||
| Barton | 17 | at | Tusculum | 41 | @ SAC | |||
| 10/30/2021 | Bluefield St WV | 7 | at | Barton | 62 | |||
| Washington and Lee | 30 | at | Emory & Henry | 28 | ODC (D3) | |||
| Newberry | 48 | at | Erskine | 10 | SAC | |||
| 11/6/2021 | Lenoir-Rhyne | 56 | at | Barton | 20 | SAC | ||
| Emory & Henry | 66 | at | Guilford | 13 | @ ODC (D3) | |||
| Erskine | 7 | at | Shorter | 38 | @ GSC | |||
| 11/13/2021 | Saint Anselm | at | Bluefield St WV | Cancelled | NE10 | |||
| Ferrum | 23 | at | Emory & Henry | 41 | ODC (D3) | |||
| Kentucky State | 41 | at | Erskine | 17 | SIAC | |||
| Barton | 36 | at | Virginia-Wise | 24 | @ SAC |