| 9/4/2021 | Massachusetts (1-11) | 7 | at | Pittsburgh | 51 | Ind | ||
| 9/11/2021 | Pittsburgh | 41 | at | Tennessee (7-6) | 34 | at SEC | ||
| 9/18/2021 | Western Michigan (8-5) | 44 | at | Pittsburgh | 41 | MAC | ||
| 9/25/2021 | New Hampshire (3-8) | 7 | at | Pittsburgh | 77 | CAAF (1AA) | ||
| 10/2/2021 | Pittsburgh | 52 | at | Georgia Tech (3-9,2-6) | 21 | |||
| 10/16/2021 | Pittsburgh | 28 | at | Virginia Tech (6-7,4-4) | 7 | |||
| 10/23/2021 | Clemson (10-3,6-2) | 17 | at | Pittsburgh | 27 | |||
| 10/30/2021 | Miami-Florida (7-5,5-3) | 38 | at | Pittsburgh | 34 | |||
| 11/6/2021 | Pittsburgh | 54 | at | Duke (3-9,0-8) | 29 | |||
| 11/11/2021 | North Carolina (6-7,4-5) | 23 | at | Pittsburgh | 30 | OT | ||
| 11/20/2021 | Virginia (6-6,4-4) | 38 | at | Pittsburgh | 48 | |||
| 11/27/2021 | Pittsburgh | 31 | at | Syracuse (5-7,2-6) | 14 | |||
| 12/4/2021 | Pittsburgh | 45 | vs | Wake Forest (11-3,7-3) | 21 | ACC Championship - Charlotte NC | ||
| 12/30/2021 | Pittsburgh | 21 | vs | Michigan State (11-2) | 31 | Peach Bowl - Atlanta GA | vs B10 |
| vs Pittsburgh | vs Other Opponents | Pittsburgh compared to OOs | |
| Record: | 3-11 | 84-77 | |
| Points Scored: | 23.64 | 29.57 | 5.93 |
| Points Allowed: | 41.43 | 28.56 | 12.87 |
| Margin: | -17.79 | 1.01 | 18.80 |
| Total Points: | 65.07 | 58.13 | 6.94 |