| 9/2/2021 | Missouri Western (6-5,5-5) | 20 | at | Central Oklahoma | 24 | | | |
| 9/11/2021 | Central Oklahoma | 21 | at | Emporia State (6-6,5-5) | 31 | | | |
| 9/18/2021 | Missouri Southern (3-8,2-8) | 14 | at | Central Oklahoma | 10 | | | |
| 9/25/2021 | Central Oklahoma | 0 | at | Northwest Missouri State (11-2,9-1) | 38 | | | |
| 10/2/2021 | Lincoln MO (0-10) | 28 | at | Central Oklahoma | 69 | | | GLV |
| 10/7/2021 | Central Oklahoma | 49 | at | Northeastern State (2-9,1-9) | 9 | | | |
| 10/16/2021 | Central Oklahoma | 24 | at | Fort Hays State (5-6,4-6) | 14 | | | |
| 10/23/2021 | Washburn (9-3,8-2) | 29 | at | Central Oklahoma | 17 | | | |
| 10/30/2021 | Central Oklahoma | 20 | at | Pittsburg State (8-3,7-3) | 26 | | | |
| 11/6/2021 | Nebraska-Kearney (10-3,8-2) | 37 | at | Central Oklahoma | 22 | | | |
| 11/13/2021 | Central Oklahoma | 29 | at | Central Missouri (4-7,3-7) | 30 | | | |