| 9/4/2021 | Villanova | 47 | at | Lehigh (3-8) | 3 | at Pat | ||
| 9/11/2021 | Bucknell (1-10) | 3 | at | Villanova | 55 | Pat | ||
| 9/18/2021 | Richmond (6-5,4-4) | 27 | at | Villanova | 34 | |||
| 9/25/2021 | Villanova | 17 | at | Penn State (7-6) | 38 | at B10 | ||
| 10/9/2021 | Villanova | 28 | at | James Madison (12-2,7-1) | 27 | |||
| 10/16/2021 | Villanova | 17 | at | Albany NY (2-9,1-7) | 10 | |||
| 10/23/2021 | Rhode Island (7-4,4-4) | 0 | at | Villanova | 44 | |||
| 10/30/2021 | William & Mary (6-5,4-4) | 31 | at | Villanova | 18 | |||
| 11/6/2021 | Villanova | 35 | at | Elon (6-5,5-3) | 0 | |||
| 11/13/2021 | Stony Brook (5-6,4-4) | 14 | at | Villanova | 33 | |||
| 11/20/2021 | Villanova | 21 | at | Delaware (5-6,3-5) | 13 | |||
| 12/3/2021 | Holy Cross (10-3) | 16 | at | Villanova | 21 | Pat | ||
| 12/11/2021 | South Dakota State (11-4) | 35 | at | Villanova | 21 | FCS quarterfinals | MVC |
| vs Villanova | vs Other Opponents | Villanova compared to OOs | |
| Record: | 3-10 | 78-63 | |
| Points Scored: | 16.69 | 25.14 | 8.45 |
| Points Allowed: | 30.08 | 22.09 | 7.99 |
| Margin: | -13.39 | 3.05 | 16.44 |
| Total Points: | 46.77 | 47.23 | -0.46 |