| 9/4/2021 | Massachusetts | 7 | at | Pittsburgh (11-3) | 51 | at ACC | ||
| 9/11/2021 | Boston College (6-6) | 45 | at | Massachusetts | 28 | ACC | ||
| 9/18/2021 | Eastern Michigan (7-6) | 42 | at | Massachusetts | 28 | MAC | ||
| 9/25/2021 | Massachusetts | 3 | at | Coastal Carolina (11-2) | 53 | at SBC | ||
| 10/2/2021 | Toledo (7-6) | 45 | at | Massachusetts | 7 | MAC | ||
| 10/9/2021 | Connecticut (1-11,0-2) | 13 | at | Massachusetts | 27 | |||
| 10/23/2021 | Massachusetts | 3 | at | Florida State (5-7) | 59 | at ACC | ||
| 10/30/2021 | Massachusetts | 17 | at | Liberty (8-5,1-1) | 62 | |||
| 11/6/2021 | Rhode Island (7-4) | 35 | at | Massachusetts | 22 | CAAF (1AA) | ||
| 11/13/2021 | Maine (6-5) | 35 | at | Massachusetts | 10 | CAAF (1AA) | ||
| 11/20/2021 | Massachusetts | 17 | at | Army (9-4,3-0) | 33 | |||
| 11/27/2021 | Massachusetts | 27 | at | New Mexico State (2-10,1-0) | 44 |
| vs Massachusetts | vs Other Opponents | Massachusetts compared to OOs | |
| Record: | 11-1 | 69-68 | |
| Points Scored: | 43.08 | 28.63 | -14.45 |
| Points Allowed: | 16.33 | 27.49 | -11.16 |
| Margin: | 26.75 | 1.14 | -25.61 |
| Total Points: | 59.41 | 56.12 | 3.29 |