Schedule:
| Game | Date | Away Team (Rank) | Away Score | Home Team (Rank) | Home Score | Game Status | Result | Margin |
|---|---|---|---|---|---|---|---|---|
| 1 | 2021-09-04 | Massachusetts | 7 | Pittsburgh | 51 | Final | L | -44 |
| 2 | 2021-09-11 | Boston College | 45 | Massachusetts | 28 | Final | L | -17 |
| 3 | 2021-09-18 | Eastern Michigan | 42 | Massachusetts | 28 | Final | L | -14 |
| 4 | 2021-09-25 | Massachusetts | 3 | Coastal Carolina | 53 | Final | L | -50 |
| 5 | 2021-10-02 | Toledo | 45 | Massachusetts | 7 | Final | L | -38 |
| 6 | 2021-10-08 | Connecticut | 0 | Massachusetts | 0 | Cancelled | - | - |
| 7 | 2021-10-09 | Connecticut | 13 | Massachusetts | 27 | Final | W | 14 |
| 8 | 2021-10-23 | Massachusetts | 3 | Florida State | 59 | Final | L | -56 |
| 9 | 2021-10-30 | Massachusetts | 17 | Liberty | 62 | Final | L | -45 |
| 10 | 2021-11-06 | Rhode Island | 35 | Massachusetts | 22 | Final | L | -13 |
| 11 | 2021-11-13 | Maine | 35 | Massachusetts | 10 | Final | L | -25 |
| 12 | 2021-11-20 | Massachusetts | 17 | Army | 33 | Final | L | -16 |
| 13 | 2021-11-27 | Massachusetts (205) | 27 | New Mexico State (156) | 44 | Final | L | -17 |