| 8/28/2021 | Iowa Wesleyan | 13 | at | Saint Ambrose | 45 | @ MSFA | ||
| 9/4/2021 | Missouri Baptist | 31 | at | Iowa Wesleyan | 7 | MSFA | ||
| 9/11/2021 | Iowa Wesleyan | 27 | at | Quincy | 59 | @ GLV (D2) | ||
| 9/18/2021 | Trinity International | 49 | at | Iowa Wesleyan | 32 | MSFA | ||
| 9/25/2021 | Valley City State | 28 | at | Iowa Wesleyan | 14 | NSAA | ||
| 10/2/2021 | Crown | 28 | at | Iowa Wesleyan | 69 | UMWAC (D3) | ||
| 10/16/2021 | Iowa Wesleyan | 6 | at | Dickinson State | 55 | @ NSAA | ||
| 10/23/2021 | Iowa Wesleyan | 15 | at | Dakota State | 53 | @ NSAA | ||
| 10/30/2021 | Presentation | 10 | at | Iowa Wesleyan | 21 | NSAA | ||
| 11/6/2021 | Waldorf | 42 | at | Iowa Wesleyan | 12 | NSAA | ||
| 11/11/2021 | Iowa Wesleyan | 14 | at | Mayville State | 42 | @ NSAA |