| 9/4/2021 | Norfolk State (6-5) | 10 | at | Toledo | 49 | MEAC (1AA) | ||
| 9/11/2021 | Toledo | 29 | at | Notre Dame (11-2) | 32 | at ND | ||
| 9/18/2021 | Colorado State (3-9) | 22 | at | Toledo | 6 | MW | ||
| 9/25/2021 | Toledo | 22 | at | Ball State (6-7,4-4) | 12 | |||
| 10/2/2021 | Toledo | 45 | at | Massachusetts (1-11) | 7 | at Ind | ||
| 10/9/2021 | Northern Illinois (9-5,7-2) | 22 | at | Toledo | 20 | |||
| 10/16/2021 | Toledo | 23 | at | Central Michigan (9-4,6-2) | 26 | OT | ||
| 10/23/2021 | Western Michigan (8-5,4-4) | 15 | at | Toledo | 34 | |||
| 11/2/2021 | Eastern Michigan (7-6,4-4) | 52 | at | Toledo | 49 | |||
| 11/10/2021 | Toledo | 49 | at | Bowling Green (4-8,2-6) | 17 | |||
| 11/16/2021 | Toledo | 35 | at | Ohio (3-9,3-5) | 23 | |||
| 11/27/2021 | Akron (2-10,1-7) | 14 | at | Toledo | 49 | |||
| 12/17/2021 | Middle Tenn State (7-6) | 31 | vs | Toledo | 24 | Bahamas Bowl - Nassau | CUSA |
| vs Toledo | vs Other Opponents | Toledo compared to OOs | |
| Record: | 6-7 | 70-80 | |
| Points Scored: | 21.77 | 27.81 | 6.04 |
| Points Allowed: | 33.38 | 29.93 | 3.45 |
| Margin: | -11.61 | -2.12 | 9.49 |
| Total Points: | 55.15 | 57.74 | -2.59 |