| 8/26/2021 | Jamestown | 7 | at | Valley City State | 24 | @ NSAA | ||
| 8/28/2021 | Dakota State | 6 | at | Dakota Wesleyan | 0 | NSAA | ||
| Sterling | 38 | at | Midland U. | 36 | KCAC | |||
| Northwestern IA | 66 | at | Presentation | 9 | @ NSAA | |||
| Briar Cliff | 3 | at | Waldorf | 30 | @ NSAA | |||
| 9/4/2021 | Doane | 17 | at | Briar Cliff | 3 | |||
| Midland U. | 25 | at | Dordt | 24 | ||||
| Concordia NE | 7 | at | Morningside | 63 | ||||
| Dakota Wesleyan | 20 | at | Mount Marty | 3 | ||||
| Hastings | 13 | at | Northwestern IA | 45 | ||||
| 9/11/2021 | Briar Cliff | 21 | at | Concordia NE | 61 | |||
| Morningside | 56 | at | Doane | 14 | ||||
| Dordt | 61 | at | Hastings | 10 | ||||
| Mount Marty | 6 | at | Jamestown | 35 | ||||
| Northwestern IA | 35 | at | Midland U. | 29 | OT | |||
| 9/18/2021 | Concordia NE | 7 | at | Dordt | 27 | |||
| Jamestown | 32 | at | Hastings | 28 | ||||
| Dakota Wesleyan | 14 | at | Midland U. | 27 | ||||
| Mount Marty | 7 | at | Morningside | 56 | ||||
| Doane | 0 | at | Northwestern IA | 38 | ||||
| 9/25/2021 | Northwestern IA | 31 | at | Concordia NE | 7 | |||
| Hastings | 16 | at | Dakota Wesleyan | 27 | ||||
| Dordt | 27 | at | Doane | 7 | ||||
| Midland U. | 33 | at | Jamestown | 22 | ||||
| Briar Cliff | 36 | at | Mount Marty | 28 | ||||
| 10/2/2021 | Hastings | 24 | at | Briar Cliff | 23 | |||
| Dakota Wesleyan | 0 | at | Concordia NE | 34 | ||||
| Jamestown | 20 | at | Doane | 44 | ||||
| Midland U. | 14 | at | Morningside | 59 | ||||
| Northwestern IA | 56 | at | Mount Marty | 17 | ||||
| 10/9/2021 | Doane | 13 | at | Dakota Wesleyan | 17 | |||
| Mount Marty | 21 | at | Dordt | 63 | ||||
| Morningside | 62 | at | Hastings | 7 | ||||
| Concordia NE | 24 | at | Jamestown | 17 | ||||
| Briar Cliff | 7 | at | Midland U. | 59 | ||||
| 10/16/2021 | Morningside | 84 | at | Briar Cliff | 7 | |||
| Hastings | 0 | at | Doane | 44 | ||||
| Dakota Wesleyan | 13 | at | Dordt | 45 | ||||
| Northwestern IA | 63 | at | Jamestown | 7 | ||||
| Concordia NE | 38 | at | Mount Marty | 7 | ||||
| 10/23/2021 | Midland U. | 7 | at | Concordia NE | 21 | |||
| Northwestern IA | 50 | at | Dakota Wesleyan | 0 | ||||
| Mount Marty | 7 | at | Doane | 28 | ||||
| Briar Cliff | 41 | at | Jamestown | 38 | ||||
| Dordt | 28 | at | Morningside | 34 | ||||
| 10/30/2021 | Dakota Wesleyan | 14 | at | Briar Cliff | 20 | |||
| Doane | 24 | at | Midland U. | 13 | ||||
| Jamestown | 7 | at | Morningside | 70 | ||||
| Hastings | 28 | at | Mount Marty | 21 | ||||
| Dordt | 28 | at | Northwestern IA | 63 | ||||
| 11/6/2021 | Doane | 13 | at | Concordia NE | 20 | |||
| Jamestown | 25 | at | Dakota Wesleyan | 31 | ||||
| Briar Cliff | 0 | at | Dordt | 58 | ||||
| Midland U. | 35 | at | Hastings | 17 | ||||
| Morningside | 55 | at | Northwestern IA | 49 | ||||
| 11/13/2021 | Northwestern IA | 63 | at | Briar Cliff | 7 | |||
| Morningside | 52 | at | Dakota Wesleyan | 7 | ||||
| Concordia NE | 17 | at | Hastings | 7 | ||||
| Dordt | 77 | at | Jamestown | 6 | ||||
| Mount Marty | 14 | at | Midland U. | 31 | ||||
| 11/20/2021 | Ottawa AZ | 38 | at | Morningside | 63 | Soon | ||
| Central Methodist | 7 | at | Northwestern IA | 24 | HAAC | |||
| 11/27/2021 | Kansas Wesleyan | 21 | at | Morningside | 58 | KCAC | ||
| Marian IN | 20 | at | Northwestern IA | 25 | MSFA | |||
| 12/4/2021 | Northwestern IA | 19 | at | Morningside | 28 | |||
| 12/18/2021 | Grand View | 28 | vs | Morningside | 38 | NAIA Championship - Durham NC | vs HAAC |