| 9/4/2021 | Northern Illinois | 22 | at | Georgia Tech (3-9) | 21 | at ACC | ||
| 9/11/2021 | Wyoming (7-6) | 50 | at | Northern Illinois | 43 | MW | ||
| 9/18/2021 | Northern Illinois | 10 | at | Michigan (12-2) | 63 | at B10 | ||
| 9/25/2021 | Maine (6-5) | 14 | at | Northern Illinois | 41 | CAAF (1AA) | ||
| 10/2/2021 | Eastern Michigan (7-6,4-4) | 20 | at | Northern Illinois | 27 | |||
| 10/9/2021 | Northern Illinois | 22 | at | Toledo (7-6,5-3) | 20 | |||
| 10/16/2021 | Bowling Green (4-8,2-6) | 26 | at | Northern Illinois | 34 | |||
| 10/23/2021 | Northern Illinois | 39 | at | Central Michigan (9-4,6-2) | 38 | |||
| 11/3/2021 | Northern Illinois | 47 | at | Kent State (7-7,6-3) | 52 | |||
| 11/10/2021 | Ball State (6-7,4-4) | 29 | at | Northern Illinois | 30 | |||
| 11/17/2021 | Northern Illinois | 33 | at | Buffalo (4-8,2-6) | 27 | OT | ||
| 11/23/2021 | Western Michigan (8-5,4-4) | 42 | at | Northern Illinois | 21 | |||
| 12/4/2021 | Kent State (7-7,6-3) | 23 | vs | Northern Illinois | 41 | MAC Championship Detroit MI | ||
| 12/17/2021 | Northern Illinois | 41 | vs | Coastal Carolina (11-2) | 47 | Tangerine Cure Bowl - Orlando FL | vs SBC |
| vs Northern Illinois | vs Other Opponents | Northern Illinois compared to OOs | |
| Record: | 5-9 | 92-72 | |
| Points Scored: | 33.71 | 30.29 | -3.42 |
| Points Allowed: | 32.21 | 27.85 | 4.36 |
| Margin: | 1.50 | 2.44 | 0.94 |
| Total Points: | 65.92 | 58.14 | 7.78 |