| 9/4/2021 | Western Michigan (8-5) | 14 | at | Michigan | 47 | | | MAC |
| 9/11/2021 | Washington (4-8) | 10 | at | Michigan | 31 | | | P12 |
| 9/18/2021 | Northern Illinois (9-5) | 10 | at | Michigan | 63 | | | MAC |
| 9/25/2021 | Rutgers (5-8,2-7) | 13 | at | Michigan | 20 | | | |
| 10/2/2021 | Michigan | 38 | at | Wisconsin (9-4,6-3) | 17 | | | |
| 10/9/2021 | Michigan | 32 | at | Nebraska (3-9,1-8) | 29 | | | |
| 10/23/2021 | Northwestern (3-9,1-8) | 7 | at | Michigan | 33 | | | |
| 10/30/2021 | Michigan | 33 | at | Michigan State (11-2,7-2) | 37 | | | |
| 11/6/2021 | Indiana (2-10,0-9) | 7 | at | Michigan | 29 | | | |
| 11/13/2021 | Michigan | 21 | at | Penn State (7-6,4-5) | 17 | | | |
| 11/20/2021 | Michigan | 59 | at | Maryland (7-6,3-6) | 18 | | | |
| 11/27/2021 | Ohio State (11-2,8-1) | 27 | at | Michigan | 42 | | | |
| 12/4/2021 | Michigan | 42 | vs | Iowa (10-4,7-3) | 3 | | Big 10 Championship - Indianapolis IN | |
| 12/31/2021 | Georgia (14-1) | 34 | vs | Michigan | 11 | | FBS Semifinal - Miami Gardens FL | SEC |