| 9/2/2021 | West Georgia | 45 | at | Carson-Newman | 7 | @ SAC | ||
| Bethel TN | 14 | at | Delta State | 48 | MSC (NAIA) | |||
| Albany State GA | 24 | at | Mississippi College | 0 | SIAC | |||
| 9/4/2021 | West Florida | 42 | at | McNeese State | 36 | @ SLC (1AA) | ||
| Limestone | 16 | at | North Greenville | 37 | SAC | |||
| Brevard | 14 | at | Shorter | 38 | USASC (D3) | |||
| Savannah State | 7 | at | Valdosta State | 53 | SIAC | |||
| Morehouse | 7 | at | West Alabama | 48 | SIAC | |||
| 9/11/2021 | Shorter | 12 | at | Albany State GA | 28 | @ SIAC | ||
| McKendree | 17 | at | Delta State | 45 | GLV | |||
| North Greenville | 24 | at | Newberry | 14 | @ SAC | |||
| West Alabama | 33 | at | Tuskegee | 7 | @ SIAC | |||
| Valdosta State | 51 | at | Virginia Union | 7 | @ CIAA | |||
| Southwest Baptist | 14 | at | West Florida | 63 | GLV | |||
| Morehouse | 0 | at | West Georgia | 47 | SIAC | |||
| 9/16/2021 | North American U | 0 | at | West Alabama | 80 | None (Unk?) | ||
| 9/18/2021 | Shorter | 38 | at | Clark Atlanta | 17 | @ SIAC | ||
| Fort Lauderdale | 0 | at | Mississippi College | 63 | None (Unk?) | |||
| West Florida | 35 | at | Texas A&M-Commerce | 17 | @ LSC | |||
| North Greenville | 13 | at | The Citadel | 45 | @ SoCon (1AA) | |||
| Albany State GA | 3 | at | Valdosta State | 21 | SIAC | |||
| Delta State | 26 | at | West Georgia | 27 | ||||
| 9/25/2021 | North Greenville | 38 | at | Erskine | 7 | @ D2Ind | ||
| Delta State | 17 | at | Jackson State | 24 | @ SWAC (1AA) | |||
| West Alabama | 31 | at | Mississippi College | 28 | ||||
| West Georgia | 56 | at | Shorter | 0 | ||||
| Fort Lauderdale | at | West Florida | Cancelled | None (Unk?) | ||||
| 10/2/2021 | West Florida | 39 | at | Delta State | 33 | |||
| Mississippi College | 42 | at | North Greenville | 21 | ||||
| Shorter | 13 | at | Valdosta State | 49 | ||||
| West Alabama | 38 | at | West Georgia | 20 | ||||
| 10/9/2021 | West Georgia | 40 | at | Mississippi College | 21 | |||
| West Florida | 52 | at | North Greenville | 10 | ||||
| West Alabama | 44 | at | Shorter | 7 | ||||
| Delta State | 0 | at | Valdosta State | 55 | ||||
| 10/16/2021 | North Greenville | 42 | at | Delta State | 34 | 2OT | ||
| Mississippi College | 20 | at | Shorter | 7 | ||||
| Valdosta State | 42 | at | West Alabama | 17 | ||||
| West Georgia | 30 | at | West Florida | 26 | ||||
| 10/23/2021 | Valdosta State | 41 | at | Mississippi College | 14 | |||
| Delta State | 35 | at | West Alabama | 30 | ||||
| Shorter | 23 | at | West Florida | 45 | ||||
| North Greenville | 12 | at | West Georgia | 34 | ||||
| 10/30/2021 | Shorter | 13 | at | Delta State | 14 | |||
| West Florida | 63 | at | Mississippi College | 28 | ||||
| West Alabama | 31 | at | North Greenville | 14 | ||||
| West Georgia | 34 | at | Valdosta State | 36 | ||||
| 11/6/2021 | Mississippi College | 21 | at | Delta State | 24 | OT | ||
| Erskine | 7 | at | Shorter | 38 | D2Ind | |||
| North Greenville | 21 | at | Valdosta State | 31 | ||||
| West Florida | 47 | at | West Alabama | 7 | ||||
| 11/13/2021 | Shorter | 0 | at | North Greenville | 56 | |||
| Mississippi College | 28 | at | West Alabama | 24 | ||||
| Valdosta State | 42 | at | West Florida | 61 | ||||
| Delta State | 7 | at | West Georgia | 44 | ||||
| 11/20/2021 | West Georgia | 23 | at | Albany State GA | 7 | @ SIAC | ||
| Newberry | 33 | at | West Florida | 30 | OT | SAC | ||
| 11/27/2021 | West Georgia | 35 | at | Valdosta State | 66 | |||
| 12/4/2021 | Bowie State | 17 | at | Valdosta State | 41 | CIAA | ||
| 12/11/2021 | Colorado Mines | 31 | at | Valdosta State | 34 | D2 Semifinal | RMAC | |
| 12/18/2021 | Valdosta State | 17 | vs | Ferris State | 58 | D2 Championship - McKinney TX | vs GLIAC |