| 9/2/2010 | Midwestern State 52 @ New Mexico Highlands Cowboys 6 | |
| 9/11/2010 | Midwestern State 44 @ Eastern New Mexico Greyhounds 17 | † |
| 9/18/2010 | Southwestern Oklahoma State Bulldogs 9 @ Midwestern State 46 | † |
| 9/25/2010 | Midwestern State 30 @ Central Oklahoma Bronchos 24 | † |
| 10/2/2010 | Incarnate Word Cardinals 31 @ Midwestern State 38 | † |
| 10/9/2010 | Midwestern State 28 @ Abilene Christian Wildcats 31 | † |
| 10/16/2010 | Angelo State Rams 21 @ Midwestern State 35 | † |
| 10/23/2010 | Midwestern State 29 @ West Texas A&M Buffaloes 42 | † |
| 10/30/2010 | Tarleton State Texans 26 @ Midwestern State 31 | † |
| 11/6/2010 | Midwestern State 7 @ Texas A&M-Kingsville Javelinas 27 | † |
| 11/13/2010 | Northeastern State Riverhawks 8 @ Midwestern State 28 | † |
| 12/4/2010 | Midwestern State 14 vs Washburn Ichabods 45 (Topeka KS) |