| 9/5/2021 | Emory & Henry (6-4) | 36 | at | North Carolina Wesleyan | 7 | D2Ind (D2) | ||
| 9/11/2021 | Shenandoah (7-3) | 30 | at | North Carolina Wesleyan | 21 | ODC | ||
| 9/18/2021 | Brevard (6-4,4-2) | 32 | at | North Carolina Wesleyan | 7 | |||
| 9/25/2021 | North Carolina Wesleyan | 26 | at | LaGrange (2-8,1-5) | 21 | |||
| 10/2/2021 | North Carolina Wesleyan | 17 | at | Averett (5-5) | 9 | at ODC | ||
| 10/9/2021 | Greensboro (0-10,0-6) | 0 | at | North Carolina Wesleyan | 21 | |||
| 10/16/2021 | Maryville (4-6,3-3) | 31 | at | North Carolina Wesleyan | 26 | |||
| 10/30/2021 | North Carolina Wesleyan | 7 | at | Huntingdon AL (8-3,6-0) | 30 | |||
| 11/6/2021 | Southern Virginia (2-8) | 10 | at | North Carolina Wesleyan | 19 | ODC | ||
| 11/13/2021 | North Carolina Wesleyan | 7 | at | Methodist (7-2,5-1) | 38 |
| vs North Carolina Wesleyan | vs Other Opponents | North Carolina Wesleyan compared to OOs | |
| Record: | 6-4 | 41-49 | |
| Points Scored: | 23.70 | 26.34 | 2.64 |
| Points Allowed: | 15.80 | 26.44 | -10.64 |
| Margin: | 7.90 | -0.10 | -8.00 |
| Total Points: | 39.50 | 52.78 | -13.28 |