| 9/2/2021 | West Georgia | 45 | at | Carson-Newman | 7 | GSC | ||
| Chowan | 30 | at | Mars Hill | 24 | OT | CIAA | ||
| Shaw | 7 | at | Wingate | 30 | CIAA | |||
| 9/4/2021 | Newberry | 31 | at | Barton | 7 | @ D2Ind | ||
| Erskine | 27 | at | Catawba | 37 | D2Ind | |||
| Limestone | 16 | at | North Greenville | 37 | @ GSC | |||
| Tusculum | 58 | at | St Augustine's | 14 | @ CIAA | |||
| Lenoir-Rhyne | 48 | at | Virginia State | 7 | @ CIAA | |||
| Virginia U-Lynchburg | 0 | at | Virginia-Wise | 54 | None (Unk?) | |||
| 9/9/2021 | Virginia U-Lynchburg | 14 | at | Mars Hill | 50 | None (Unk?) | ||
| 9/11/2021 | Winston-Salem State | 6 | at | Catawba | 28 | CIAA | ||
| Virginia-Wise | 14 | at | East Tennessee St | 45 | @ SoCon (1AA) | |||
| St Augustine's | at | Limestone | Cancelled | CIAA | ||||
| North Greenville | 24 | at | Newberry | 14 | GSC | |||
| Chowan | 46 | at | Tusculum | 38 | 2OT | CIAA | ||
| Fayetteville State | 21 | at | Wingate | 40 | CIAA | |||
| 9/18/2021 | Wingate | 25 | at | Carson-Newman | 3 | |||
| Barton | 10 | at | Catawba | 17 | D2Ind | |||
| Virginia-Wise | 9 | at | Mars Hill | 44 | ||||
| Lenoir-Rhyne | 21 | at | Newberry | 28 | ||||
| Limestone | 21 | at | Tusculum | 24 | ||||
| 9/25/2021 | Mars Hill | 16 | at | Lenoir-Rhyne | 31 | |||
| Barton | 45 | at | Limestone | 7 | D2Ind | |||
| Newberry | 24 | at | Tusculum | 19 | ||||
| Carson-Newman | 7 | at | Virginia-Wise | 33 | ||||
| Catawba | at | Wingate | Cancelled | |||||
| 10/2/2021 | Carson-Newman | 17 | at | Barton | 31 | @ D2Ind | ||
| Limestone | at | Catawba | Canceled | |||||
| Newberry | 22 | at | Mars Hill | 28 | 2OT | |||
| Lenoir-Rhyne | 28 | at | Virginia-Wise | 35 | ||||
| Tusculum | 35 | at | Wingate | 43 | ||||
| 10/9/2021 | Carson-Newman | 27 | at | Catawba | 33 | |||
| Tusculum | 31 | at | Lenoir-Rhyne | 38 | ||||
| Wingate | 35 | at | Limestone | 17 | ||||
| Barton | 32 | at | Mars Hill | 40 | D2Ind | |||
| Newberry | 37 | at | Virginia-Wise | 14 | ||||
| 10/16/2021 | Wingate | 20 | at | Barton | 26 | OT | @ D2Ind | |
| Lenoir-Rhyne | 59 | at | Carson-Newman | 0 | ||||
| Mars Hill | 32 | at | Limestone | 3 | ||||
| Catawba | 7 | at | Newberry | 14 | ||||
| Virginia-Wise | 21 | at | Tusculum | 37 | ||||
| 10/23/2021 | Limestone | 3 | at | Lenoir-Rhyne | 45 | |||
| Catawba | 14 | at | Mars Hill | 31 | ||||
| Carson-Newman | 3 | at | Newberry | 34 | ||||
| Barton | 17 | at | Tusculum | 41 | D2Ind | |||
| Wingate | 48 | at | Virginia-Wise | 21 | ||||
| 10/30/2021 | Mars Hill | 49 | at | Carson-Newman | 23 | |||
| Tusculum | 28 | at | Catawba | 31 | ||||
| Newberry | 48 | at | Erskine | 10 | @ D2Ind | |||
| Virginia-Wise | 28 | at | Limestone | 24 | ||||
| Lenoir-Rhyne | 31 | at | Wingate | 6 | ||||
| 11/6/2021 | Lenoir-Rhyne | 56 | at | Barton | 20 | @ D2Ind | ||
| Limestone | 21 | at | Carson-Newman | 27 | ||||
| Virginia-Wise | 30 | at | Catawba | 7 | ||||
| Tusculum | 7 | at | Mars Hill | 20 | ||||
| Wingate | 35 | at | Newberry | 41 | 2OT | |||
| 11/13/2021 | Catawba | 3 | at | Lenoir-Rhyne | 56 | |||
| Newberry | 42 | at | Limestone | 7 | ||||
| Carson-Newman | 13 | at | Tusculum | 48 | ||||
| Barton | 36 | at | Virginia-Wise | 24 | D2Ind | |||
| Mars Hill | 19 | at | Wingate | 26 | ||||
| 11/20/2021 | Lenoir-Rhyne | 10 | at | Bowie State | 31 | @ CIAA | ||
| Newberry | 33 | at | West Florida | 30 | OT | @ GSC | ||
| 11/27/2021 | Newberry | 10 | at | Bowie State | 13 | @ CIAA |