| 9/2/2021 | Henderson State (9-2,9-2) | 31 | at | Southwestern Oklahoma State | 13 | | | |
| 9/11/2021 | Southwestern Oklahoma State | 27 | at | Southern Arkansas (4-7,4-7) | 42 | | | |
| 9/18/2021 | Southwestern Oklahoma State | 28 | at | Southeastern Oklahoma State (9-3,8-3) | 37 | | | |
| 9/25/2021 | Oklahoma Baptist (8-4,7-4) | 31 | at | Southwestern Oklahoma State | 27 | | | |
| 10/2/2021 | Southwestern Oklahoma State | 16 | at | Arkansas-Monticello (5-6,5-6) | 18 | | | |
| 10/9/2021 | Ouachita (9-2,9-2) | 30 | at | Southwestern Oklahoma State | 10 | | | |
| 10/14/2021 | Southwestern Oklahoma State | 22 | at | Southern Nazarene (1-10,1-10) | 30 | | | |
| 10/23/2021 | East Central (7-4,7-4) | 44 | at | Southwestern Oklahoma State | 34 | | | |
| 10/30/2021 | Arkansas Tech (4-7,4-7) | 15 | at | Southwestern Oklahoma State | 14 | | | |
| 11/6/2021 | Southwestern Oklahoma State | 7 | at | Harding (11-2,10-1) | 55 | | | |
| 11/13/2021 | Southwestern Oklahoma State | 28 | at | Northwestern Oklahoma State (2-9,2-9) | 31 | | | |