| 9/2/2021 | Findlay | 14 | at | Ferris State | 54 | GMAC | ||
| Gannon | 28 | at | Northwood | 21 | OT | PSAC | ||
| Slippery Rock | 24 | at | Wayne State MI | 21 | PSAC | |||
| 9/4/2021 | Truman State | 31 | at | Davenport | 14 | GLV | ||
| Northern Michigan | 27 | at | McKendree | 20 | @ GLV | |||
| Hillsdale | 10 | at | Michigan Tech | 14 | GMAC | |||
| Texas A&M-Kingsville | 9 | at | Saginaw Valley State | 13 | LSC | |||
| 9/11/2021 | Ferris State | 45 | at | Ashland | 19 | @ GMAC | ||
| Saginaw Valley State | 19 | at | Bowie State | 28 | @ CIAA | |||
| Colorado State-Pueblo | 14 | at | Grand Valley State | 34 | RMAC | |||
| St Thomas | 12 | at | Michigan Tech | 9 | Pio (1AA) | |||
| Wisconsin-Oshkosh | 28 | at | Northern Michigan | 10 | WIAC (D3) | |||
| Northwood | 6 | at | Tiffin | 40 | @ GMAC | |||
| Davenport | 10 | at | Walsh | 6 | @ GMAC | |||
| Truman State | 27 | at | Wayne State MI | 9 | GLV | |||
| 9/18/2021 | Saginaw Valley State | 45 | at | Ferris State | 47 | OT | ||
| Wisconsin-La Crosse | 24 | at | Grand Valley State | 45 | WIAC (D3) | |||
| Wayne State MI | 45 | at | Missouri S&T | 51 | OT | @ GLV | ||
| Davenport | 14 | at | Northern Michigan | 20 | ||||
| 9/25/2021 | Davenport | 0 | at | Ferris State | 38 | |||
| Grand Valley State | 44 | at | Michigan Tech | 21 | ||||
| Northern Michigan | 20 | at | Northwood | 37 | ||||
| Saginaw Valley State | 41 | at | Wayne State MI | 21 | ||||
| 10/2/2021 | Davenport | 7 | at | Michigan Tech | 31 | |||
| Wayne State MI | 19 | at | Northern Michigan | 26 | ||||
| Ferris State | 67 | at | Northwood | 25 | ||||
| Grand Valley State | 49 | at | Saginaw Valley State | 17 | ||||
| 10/9/2021 | Northern Michigan | 13 | at | Davenport | 18 | |||
| Northwood | 9 | at | Grand Valley State | 70 | ||||
| Saginaw Valley State | 20 | at | Texas A&M-Commerce | 17 | OT | @ LSC | ||
| Michigan Tech | 30 | at | Wayne State MI | 27 | ||||
| 10/16/2021 | Wayne State MI | 16 | at | Davenport | 3 | |||
| Ferris State | 35 | at | Grand Valley State | 28 | ||||
| Michigan Tech | 21 | at | Northern Michigan | 14 | ||||
| Northwood | 13 | at | Saginaw Valley State | 31 | ||||
| 10/23/2021 | Ferris State | 38 | at | Michigan Tech | 10 | |||
| Grand Valley State | 28 | at | Northern Michigan | 24 | ||||
| Davenport | 21 | at | Northwood | 14 | ||||
| Wayne State MI | 25 | at | Saginaw Valley State | 41 | ||||
| 10/30/2021 | Saginaw Valley State | 24 | at | Davenport | 3 | |||
| Northern Michigan | 24 | at | Ferris State | 44 | ||||
| Michigan Tech | 9 | at | Grand Valley State | 14 | ||||
| Northwood | 21 | at | Wayne State MI | 56 | ||||
| 11/6/2021 | Ferris State | 50 | at | Davenport | 14 | |||
| Michigan Tech | 34 | at | Northwood | 0 | ||||
| Northern Michigan | 21 | at | Saginaw Valley State | 33 | ||||
| Grand Valley State | 62 | at | Wayne State MI | 13 | ||||
| 11/13/2021 | Wayne State MI | 13 | at | Ferris State | 35 | |||
| Davenport | 0 | at | Grand Valley State | 42 | ||||
| Saginaw Valley State | 20 | at | Michigan Tech | 21 | ||||
| Northwood | 26 | at | Northern Michigan | 34 | ||||
| 11/20/2021 | Lindenwood | 3 | at | Grand Valley State | 20 | MAIAA | ||
| 11/27/2021 | Grand Valley State | 20 | at | Ferris State | 54 | |||
| 12/4/2021 | Northwest Missouri State | 20 | at | Ferris State | 41 | MAIAA | ||
| 12/11/2021 | Shepherd | 7 | at | Ferris State | 55 | D2 Semifinal | PSAC | |
| 12/18/2021 | Valdosta State | 17 | vs | Ferris State | 58 | D2 Championship - McKinney TX | vs GSC |