Schedule:
| Game | Date | Away Team (Rank) | Away Score | Home Team (Rank) | Home Score | Game Status | Result | Margin |
|---|---|---|---|---|---|---|---|---|
| 1 | 2021-09-11 | Eastern Michigan | 7 | Wisconsin | 34 | Final | L | -27 |
| 2 | 2021-09-18 | Eastern Michigan | 42 | Massachusetts | 28 | Final | W | 14 |
| 3 | 2021-09-25 | Texas State | 21 | Eastern Michigan | 59 | Final | W | 38 |
| 4 | 2021-10-02 | Eastern Michigan | 20 | Northern Illinois | 27 | Final | L | -7 |
| 5 | 2021-10-09 | Miami (OH) | 12 | Eastern Michigan | 13 | Final | W | 1 |
| 6 | 2021-10-16 | Ball State | 38 | Eastern Michigan | 31 | Final | L | -7 |
| 7 | 2021-10-23 | Eastern Michigan | 55 | Bowling Green | 24 | Final | W | 31 |
| 8 | 2021-11-02 | Eastern Michigan | 52 | Toledo | 49 | Final | W | 3 |
| 9 | 2021-11-09 | Ohio | 34 | Eastern Michigan | 26 | Final | L | -8 |
| 10 | 2021-11-16 | Western Michigan | 21 | Eastern Michigan | 22 | Final | W | 1 |
| 11 | 2021-11-26 | Eastern Michigan (83) | 10 | Central Michigan (59) | 31 | Final | L | -21 |
| 12 | 2021-12-18 | Eastern Michigan (87) | 20 | Liberty (53) | 56 | Final | L | -36 |