| 9/4/2010 | Sioux Falls 41 @ Northwestern IA Red Raiders 24 | † |
| 9/11/2010 | Sioux Falls 37 @ Midland Lutheran Warriors 7 | † |
| 9/18/2010 | Doane Tigers 13 @ Sioux Falls 66 | † |
| 9/25/2010 | Sioux Falls 34 @ Hastings Broncos 10 | † |
| 10/2/2010 | Nebraska Wesleyan Prairie Wolves 0 @ Sioux Falls 44 | † |
| 10/9/2010 | Sioux Falls 66 @ Briar Cliff Chargers 21 | † |
| 10/16/2010 | Morningside Mustangs 3 @ Sioux Falls 28 | † |
| 10/23/2010 | Dakota Wesleyan Tigers 3 @ Sioux Falls 63 | † |
| 11/6/2010 | Sioux Falls 49 @ Dordt Defenders 0 | † |
| 11/13/2010 | Concordia NE Bulldogs 7 @ Sioux Falls 44 | † |
| 11/20/2010 | Northwestern Oklahoma State Rangers 14 @ Sioux Falls 33 | |
| 11/27/2010 | McKendree Bearcats 7 @ Sioux Falls 27 | |
| 12/4/2010 | MidAmerica Nazarene Pioneers 0 @ Sioux Falls 38 | |
| 12/18/2010 | Carroll MT Saints 10 vs Sioux Falls 7 (Rome GA - NAIA Championship) |