| 9/4/2021 | Greensboro (0-10) | 7 | at | Guilford | 21 | USASC | ||
| 9/11/2021 | Guilford | at | Methodist (7-2) | Postponed | at USASC | |||
| 9/18/2021 | Guilford | 7 | at | Washington and Lee (8-3,5-1) | 63 | |||
| 9/25/2021 | Hampden-Sydney (5-5,4-2) | 28 | at | Guilford | 27 | |||
| 10/2/2021 | Guilford | at | Apprentice (1-7) | Canceled | at None | |||
| 10/9/2021 | Shenandoah (7-3,3-3) | 52 | at | Guilford | 25 | |||
| 10/16/2021 | Randolph-Macon (9-1,5-1) | 58 | at | Guilford | 0 | |||
| 10/30/2021 | Guilford | 35 | at | Ferrum (6-4,4-3) | 57 | |||
| 11/6/2021 | Emory & Henry (6-4) | 66 | at | Guilford | 13 | D2Ind (D2) | ||
| 11/13/2021 | Guilford | 0 | at | Bridgewater VA (4-6,2-5) | 43 |
| vs Guilford | vs Other Opponents | Guilford compared to OOs | |
| Record: | 7-1 | 46-44 | |
| Points Scored: | 46.75 | 25.60 | -21.15 |
| Points Allowed: | 16.00 | 25.58 | -9.58 |
| Margin: | 30.75 | 0.02 | -30.73 |
| Total Points: | 62.75 | 51.18 | 11.57 |