| 9/4/2021 | Morehead State (7-4) | 10 | at | James Madison | 68 | Pio | ||
| 9/11/2021 | Maine (6-5,4-4) | 7 | at | James Madison | 55 | |||
| 9/18/2021 | James Madison | 37 | at | Weber State (6-5) | 24 | at BSky | ||
| 10/2/2021 | James Madison | 23 | at | New Hampshire (3-8,2-6) | 21 | |||
| 10/9/2021 | Villanova (10-3,7-1) | 28 | at | James Madison | 27 | |||
| 10/16/2021 | James Madison | 19 | at | Richmond (6-5,4-4) | 3 | |||
| 10/23/2021 | James Madison | 22 | at | Delaware (5-6,3-5) | 10 | |||
| 10/30/2021 | Elon (6-5,5-3) | 21 | at | James Madison | 45 | |||
| 11/6/2021 | Campbell (3-8) | 14 | at | James Madison | 51 | BigS | ||
| 11/13/2021 | James Madison | 32 | at | William & Mary (6-5,4-4) | 22 | |||
| 11/20/2021 | Towson (4-7,3-5) | 10 | at | James Madison | 56 | |||
| 12/4/2021 | Southeastern Louisiana (9-4) | 20 | at | James Madison | 59 | SLC | ||
| 12/10/2021 | Montana (10-3) | 6 | at | James Madison | 28 | FCS quarterfinals | BSky | |
| 12/17/2021 | James Madison | 14 | at | North Dakota State (14-1) | 20 | FCS semifinal | at MVC |
| vs James Madison | vs Other Opponents | James Madison compared to OOs | |
| Record: | 2-12 | 93-57 | |
| Points Scored: | 15.43 | 28.71 | 13.28 |
| Points Allowed: | 38.29 | 22.09 | 16.20 |
| Margin: | -22.86 | 6.62 | 29.48 |
| Total Points: | 53.72 | 50.80 | 2.92 |