| 9/2/2021 | Houston Baptist | 17 | at | New Mexico | 27 | @ MW (1A) | ||
| Incarnate Word | 41 | at | Youngstown State | 44 | OT | @ MVC | ||
| 9/4/2021 | West Florida | 42 | at | McNeese State | 36 | GSC (D2) | ||
| Nicholls State | 17 | at | Memphis | 42 | @ AAC (1A) | |||
| Southeastern Louisiana | 49 | at | North Alabama | 28 | @ BigS | |||
| Northwestern State | 14 | at | North Texas | 44 | @ CUSA (1A) | |||
| 9/11/2021 | Northwestern State | 10 | at | Alcorn State | 13 | @ SWAC | ||
| Northern Colorado | 45 | at | Houston Baptist | 13 | BSky | |||
| Prairie View | 9 | at | Incarnate Word | 40 | SWAC | |||
| Southeastern Louisiana | 42 | at | Louisiana Tech | 45 | @ CUSA (1A) | |||
| Nicholls State | 24 | at | UL Lafayette | 27 | @ SBC (1A) | |||
| McNeese State | 7 | at | LSU | 34 | @ SEC (1A) | |||
| 9/18/2021 | Southeastern Louisiana | 56 | at | Central Conn | 10 | @ NE | ||
| Tennessee-Martin | 35 | at | Northwestern State | 10 | OVC | |||
| Houston Baptist | 27 | at | Prairie View | 37 | @ SWAC | |||
| McNeese State | 31 | at | Southern | 24 | @ SWAC | |||
| Incarnate Word | 42 | at | Texas State | 34 | @ SBC (1A) | |||
| 9/25/2021 | McNeese State | 0 | at | Incarnate Word | 31 | |||
| North Alabama | 14 | at | Nicholls State | 31 | BigS | |||
| 10/2/2021 | Southeastern Louisiana | 38 | at | McNeese State | 35 | |||
| Houston Baptist | 17 | at | Nicholls State | 48 | ||||
| Incarnate Word | 38 | at | Northwestern State | 27 | ||||
| 10/9/2021 | Northwestern State | 21 | at | Houston Baptist | 17 | |||
| Southeastern Louisiana | 58 | at | Nicholls State | 48 | ||||
| 10/16/2021 | Nicholls State | 21 | at | Incarnate Word | 38 | |||
| McNeese State | 35 | at | Northwestern State | 17 | ||||
| Houston Baptist | 24 | at | Southeastern Louisiana | 61 | ||||
| 10/23/2021 | Nicholls State | 44 | at | Houston Baptist | 14 | |||
| Incarnate Word | 20 | at | McNeese State | 28 | ||||
| Southeastern Louisiana | 51 | at | Northwestern State | 14 | ||||
| 10/30/2021 | Houston Baptist | 21 | at | Incarnate Word | 49 | |||
| Northwestern State | 21 | at | Nicholls State | 42 | ||||
| McNeese State | 20 | at | Southeastern Louisiana | 23 | ||||
| 11/6/2021 | Southeastern Louisiana | 52 | at | Incarnate Word | 55 | |||
| Nicholls State | 24 | at | McNeese State | 14 | ||||
| Houston Baptist | 24 | at | Northwestern State | 28 | ||||
| 11/13/2021 | McNeese State | 44 | at | Houston Baptist | 3 | |||
| Incarnate Word | 27 | at | Nicholls State | 23 | ||||
| Northwestern State | 28 | at | Southeastern Louisiana | 56 | ||||
| 11/18/2021 | Nicholls State | 45 | at | Southeastern Louisiana | 42 | |||
| 11/20/2021 | Incarnate Word | 55 | at | Houston Baptist | 14 | |||
| Northwestern State | 24 | at | McNeese State | 20 | ||||
| 11/27/2021 | Stephen F. Austin | 28 | at | Incarnate Word | 35 | OT | WAC | |
| Florida A&M | 14 | at | Southeastern Louisiana | 38 | SWAC | |||
| 12/4/2021 | Southeastern Louisiana | 20 | at | James Madison | 59 | @ CAAF | ||
| Incarnate Word | 42 | at | Sam Houston | 49 | @ WAC |