| 9/2/2010 | Valparaiso Crusaders 0 @ Western Illinois 45 | |
| 9/11/2010 | Western Illinois 21 @ Purdue Boilermakers 31 | |
| 9/18/2010 | Sam Houston Bearkats 14 @ Western Illinois 56 | |
| 9/25/2010 | Indiana State Sycamores 7 @ Western Illinois 40 | † |
| 10/2/2010 | Western Illinois 28 @ North Dakota State Bison 16 | † |
| 10/9/2010 | Western Illinois 29 @ South Dakota State Jackrabbits 33 | † |
| 10/16/2010 | Youngstown State Penguins 38 @ Western Illinois 40 | † |
| 10/23/2010 | Western Illinois 28 @ Missouri State Bears 31 | † |
| 10/30/2010 | Illinois State Redbirds 38 @ Western Illinois 65 | † |
| 11/13/2010 | Western Illinois 10 @ Southern Illinois Salukis 20 | † |
| 11/20/2010 | Northern Iowa Panthers 14 @ Western Illinois 30 | † |
| 11/27/2010 | Western Illinois 17 @ Coastal Carolina Chanticleers 10 (FBS Playoffs) | |
| 12/4/2010 | Western Illinois 14 @ Appalachian State Mountaineers 42 |