| 8/26/2021 | Jamestown | 7 | at | Valley City State | 24 | GPAC | ||
| 8/28/2021 | Dakota State | 6 | at | Dakota Wesleyan | 0 | @ GPAC | ||
| Northwestern IA | 66 | at | Presentation | 9 | GPAC | |||
| Mayville State | 32 | at | Roosevelt | 37 | @ MSFA | |||
| Briar Cliff | 3 | at | Waldorf | 30 | GPAC | |||
| 9/2/2021 | Dickinson State | 24 | at | Black Hills State | 30 | @ RMAC (D2) | ||
| 9/4/2021 | Valley City State | 35 | at | Concordia-Moorhead | 32 | @ MIA (D3) | ||
| Wisconsin-La Crosse | 42 | at | Dakota State | 21 | WIAC (D3) | |||
| Wisconsin-Stevens Point | 31 | at | Mayville State | 14 | WIAC (D3) | |||
| Wisconsin-Stout | 42 | at | Presentation | 14 | WIAC (D3) | |||
| Waldorf | 24 | at | Saint Ambrose | 17 | @ MSFA | |||
| 9/11/2021 | Presentation | 14 | at | Concordia-Moorhead | 55 | @ MIA (D3) | ||
| Montana-Western | 42 | at | Dickinson State | 30 | Front | |||
| Mayville State | 7 | at | South Dakota Tech | 52 | @ RMAC (D2) | |||
| 9/18/2021 | Presentation | 13 | at | Dakota State | 40 | |||
| Dickinson State | 51 | at | Mayville State | 13 | ||||
| Waldorf | 7 | at | Valley City State | 14 | ||||
| 9/25/2021 | Mayville State | 16 | at | Dakota State | 20 | |||
| Valley City State | 28 | at | Iowa Wesleyan | 14 | @ NAIAInd | |||
| Waldorf | 38 | at | Presentation | 22 | ||||
| 10/2/2021 | Presentation | 14 | at | Dickinson State | 70 | |||
| Mayville State | 0 | at | Valley City State | 49 | ||||
| Dakota State | 21 | at | Waldorf | 26 | ||||
| 10/9/2021 | Dakota State | 14 | at | Dickinson State | 34 | |||
| Waldorf | 52 | at | Mayville State | 51 | ||||
| Valley City State | 44 | at | Presentation | 10 | ||||
| 10/16/2021 | Valley City State | 10 | at | Dakota State | 24 | |||
| Iowa Wesleyan | 6 | at | Dickinson State | 55 | NAIAInd | |||
| Presentation | 27 | at | Mayville State | 49 | ||||
| 10/23/2021 | Iowa Wesleyan | 15 | at | Dakota State | 53 | NAIAInd | ||
| Dickinson State | 14 | at | Valley City State | 7 | ||||
| Mayville State | 19 | at | Waldorf | 39 | ||||
| 10/30/2021 | Mayville State | 7 | at | Dickinson State | 53 | |||
| Presentation | 10 | at | Iowa Wesleyan | 21 | @ NAIAInd | |||
| Valley City State | 21 | at | Waldorf | 14 | ||||
| 11/6/2021 | Waldorf | 42 | at | Iowa Wesleyan | 12 | @ NAIAInd | ||
| Dickinson State | 41 | at | Presentation | 17 | ||||
| Dakota State | 7 | at | Valley City State | 33 | ||||
| 11/11/2021 | Iowa Wesleyan | 14 | at | Mayville State | 42 | NAIAInd | ||
| 11/13/2021 | Dakota State | 16 | at | Presentation | 14 | |||
| Dickinson State | 48 | at | Waldorf | 7 | ||||
| 11/20/2021 | Dickinson State | 13 | at | Grand View | 38 | @ HAAC |