| 9/2/2021 | Henderson State | 31 | at | Southwestern Oklahoma State (0-11,0-11) | 13 | | | |
| 9/11/2021 | Northwestern Oklahoma State (2-9,2-9) | 7 | at | Henderson State | 55 | | | |
| 9/18/2021 | Henderson State | 58 | at | Arkansas-Monticello (5-6,5-6) | 18 | | | |
| 9/25/2021 | Southern Arkansas (4-7,4-7) | 49 | at | Henderson State | 56 | | | |
| 10/2/2021 | Henderson State | 27 | at | Southeastern Oklahoma State (9-3,8-3) | 24 | | | |
| 10/9/2021 | East Central (7-4,7-4) | 24 | at | Henderson State | 59 | | | |
| 10/16/2021 | Harding (11-2,10-1) | 46 | at | Henderson State | 21 | | | |
| 10/23/2021 | Henderson State | 41 | at | Arkansas Tech (4-7,4-7) | 38 | | | |
| 10/30/2021 | Southern Nazarene (1-10,1-10) | 3 | at | Henderson State | 34 | | | |
| 11/6/2021 | Henderson State | 36 | at | Oklahoma Baptist (8-4,7-4) | 34 | | | |
| 11/13/2021 | Henderson State | 28 | at | Ouachita (9-2,9-2) | 31 | | | |