| 9/2/2021 | Missouri Southern | 0 | at | Nebraska-Kearney (10-3,8-2) | 38 | | | |
| 9/11/2021 | Northeastern State (2-9,1-9) | 21 | at | Missouri Southern | 17 | | | |
| 9/18/2021 | Missouri Southern | 14 | at | Central Oklahoma (4-7,3-7) | 10 | | | |
| 9/25/2021 | Fort Hays State (5-6,4-6) | 42 | at | Missouri Southern | 21 | | | |
| 10/2/2021 | Pittsburg State (8-3,7-3) | 20 | at | Missouri Southern | 16 | | | |
| 10/9/2021 | Missouri Southern | 52 | at | Lincoln MO (0-10) | 32 | | | at GLV |
| 10/16/2021 | Central Missouri (4-7,3-7) | 28 | at | Missouri Southern | 30 | | | |
| 10/23/2021 | Missouri Southern | 21 | at | Emporia State (6-6,5-5) | 24 | | | |
| 10/30/2021 | Missouri Western (6-5,5-5) | 45 | at | Missouri Southern | 28 | | | |
| 11/6/2021 | Northwest Missouri State (11-2,9-1) | 49 | at | Missouri Southern | 7 | | | |
| 11/13/2021 | Missouri Southern | 28 | at | Washburn (9-3,8-2) | 38 | | | |