Schedule:
| Game | Date | Away Team (Rank) | Away Score | Home Team (Rank) | Home Score | Game Status | Result | Margin |
|---|---|---|---|---|---|---|---|---|
| 1 | 2021-09-04 | Norfolk State | 10 | Toledo | 49 | Final | W | 39 |
| 2 | 2021-09-11 | Toledo | 29 | Notre Dame | 32 | Final | L | -3 |
| 3 | 2021-09-18 | Colorado State | 22 | Toledo | 6 | Final | L | -16 |
| 4 | 2021-09-25 | Toledo | 22 | Ball State | 12 | Final | W | 10 |
| 5 | 2021-10-02 | Toledo | 45 | Massachusetts | 7 | Final | W | 38 |
| 6 | 2021-10-09 | Northern Illinois | 22 | Toledo | 20 | Final | L | -2 |
| 7 | 2021-10-16 | Toledo | 23 | Central Michigan | 26 | Final(OT) | L | -3 |
| 8 | 2021-10-23 | Western Michigan | 15 | Toledo | 34 | Final | W | 19 |
| 9 | 2021-11-02 | Eastern Michigan | 52 | Toledo | 49 | Final | L | -3 |
| 10 | 2021-11-10 | Toledo | 49 | Bowling Green | 17 | Final | W | 32 |
| 11 | 2021-11-16 | Toledo | 35 | Ohio | 23 | Final | W | 12 |
| 12 | 2021-11-27 | Akron (157) | 14 | Toledo (72) | 49 | Final | W | 35 |
| 13 | 2021-12-17 | Middle Tennessee (88) | 31 | Toledo (84) | 24 | Final | L | -7 |