| 9/2/2021 | William Jewell | 3 | at | Colorado Mesa | 40 | @ RMAC | ||
| Washburn | 76 | at | Lincoln MO | 12 | MAIAA | |||
| Missouri S&T | 31 | at | South Dakota Tech | 34 | @ RMAC | |||
| 9/4/2021 | Truman State | 31 | at | Davenport | 14 | @ GLIAC | ||
| Northern Michigan | 27 | at | McKendree | 20 | GLIAC | |||
| Midwestern State | 48 | at | Quincy | 27 | LSC | |||
| Indianapolis | 34 | at | St Xavier | 10 | @ MSFA (NAIA) | |||
| Texas-Permian Basin | 24 | at | Southwest Baptist | 16 | LSC | |||
| 9/9/2021 | Lincoln MO | at | Northwest Missouri State | Cancelled | @ MAIAA | |||
| 9/11/2021 | McKendree | 17 | at | Delta State | 45 | @ GSC | ||
| Indianapolis | 35 | at | Hillsdale | 31 | @ GMAC | |||
| Arkansas Baptist | 0 | at | Missouri S&T | 71 | None (Unk?) | |||
| Iowa Wesleyan | 27 | at | Quincy | 59 | NAIAInd (NAIA) | |||
| Truman State | 27 | at | Wayne State MI | 9 | @ GLIAC | |||
| Southwest Baptist | 14 | at | West Florida | 63 | @ GSC | |||
| Black Hills State | 31 | at | William Jewell | 21 | RMAC | |||
| 9/18/2021 | Lincoln MO | 0 | at | Fort Hays State | 72 | @ MAIAA | ||
| Tiffin | 20 | at | Indianapolis | 17 | GMAC | |||
| Lake Erie | 17 | at | McKendree | 10 | GMAC | |||
| Wayne State MI | 45 | at | Missouri S&T | 51 | OT | GLIAC | ||
| Walsh | 17 | at | Quincy | 38 | GMAC | |||
| Findlay | 62 | at | Southwest Baptist | 41 | GMAC | |||
| Hillsdale | 24 | at | Truman State | 38 | GMAC | |||
| Ohio Dominican | 35 | at | William Jewell | 25 | GMAC | |||
| 9/25/2021 | Quincy | 23 | at | Ashland | 63 | @ GMAC | ||
| Missouri S&T | 31 | at | Hillsdale | 38 | @ GMAC | |||
| Ohio Dominican | 19 | at | Indianapolis | 16 | GMAC | |||
| William Jewell | 21 | at | Kentucky Wesleyan | 41 | @ GMAC | |||
| Southwest Baptist | 28 | at | Lake Erie | 20 | @ GMAC | |||
| Northeastern State | 49 | at | Lincoln MO | 48 | MAIAA | |||
| Truman State | 38 | at | Tiffin | 35 | @ GMAC | |||
| McKendree | 24 | at | Walsh | 10 | @ GMAC | |||
| 10/2/2021 | Lincoln MO | 28 | at | Central Oklahoma | 69 | @ MAIAA | ||
| William Jewell | 10 | at | McKendree | 52 | ||||
| Missouri S&T | 28 | at | Quincy | 31 | ||||
| Indianapolis | 77 | at | Southwest Baptist | 10 | ||||
| Lindenwood | 31 | at | Truman State | 21 | MAIAA | |||
| 10/9/2021 | McKendree | 28 | at | Indianapolis | 57 | |||
| Missouri Southern | 52 | at | Lincoln MO | 32 | MAIAA | |||
| Quincy | 28 | at | Lindenwood | 33 | @ MAIAA | |||
| Truman State | 38 | at | Missouri S&T | 21 | ||||
| Southwest Baptist | 55 | at | William Jewell | 10 | ||||
| 10/16/2021 | Lindenwood | 28 | at | Indianapolis | 20 | MAIAA | ||
| William Jewell | 16 | at | Missouri S&T | 37 | ||||
| Lincoln MO | 7 | at | Pittsburg State | 59 | @ MAIAA | |||
| McKendree | 51 | at | Quincy | 48 | ||||
| Truman State | 21 | at | Southwest Baptist | 27 | ||||
| 10/23/2021 | Southwest Baptist | 24 | at | Lindenwood | 48 | @ MAIAA | ||
| Missouri S&T | 37 | at | McKendree | 31 | ||||
| Lincoln MO | 0 | at | Nebraska-Kearney | 56 | @ MAIAA | |||
| Indianapolis | 70 | at | Quincy | 21 | ||||
| William Jewell | 0 | at | Truman State | 52 | ||||
| 10/30/2021 | Central Missouri | 77 | at | Lincoln MO | 35 | MAIAA | ||
| Indianapolis | 28 | at | Missouri S&T | 31 | ||||
| McKendree | 45 | at | Southwest Baptist | 42 | ||||
| Quincy | 28 | at | Truman State | 49 | ||||
| Lindenwood | 53 | at | William Jewell | 10 | MAIAA | |||
| 11/6/2021 | Lincoln MO | 21 | at | Emporia State | 56 | @ MAIAA | ||
| William Jewell | 14 | at | Indianapolis | 45 | ||||
| Truman State | 44 | at | McKendree | 13 | ||||
| Lindenwood | 43 | at | Missouri S&T | 16 | MAIAA | |||
| Southwest Baptist | 47 | at | Quincy | 31 | ||||
| 11/13/2021 | Missouri Western | 41 | at | Lincoln MO | 12 | MAIAA | ||
| McKendree | 30 | at | Lindenwood | 45 | @ MAIAA | |||
| Missouri S&T | 42 | at | Southwest Baptist | 41 | ||||
| Indianapolis | 13 | at | Truman State | 10 | ||||
| Quincy | 51 | at | William Jewell | 17 | ||||
| 12/4/2021 | Truman State | 34 | at | Hillsdale | 17 | @ GMAC |