| 9/4/2010 | Western Kentucky 10 @ Nebraska Cornhuskers 49 | |
| 9/11/2010 | Western Kentucky 28 @ Kentucky Wildcats 63 | |
| 9/18/2010 | Indiana Hoosiers 38 @ Western Kentucky 21 | |
| 9/25/2010 | Western Kentucky 12 @ South Florida Bulls 24 | |
| 10/9/2010 | Western Kentucky 21 @ Florida Intl Golden Panthers 28 | † |
| 10/16/2010 | UL Monroe Warhawks 35 @ Western Kentucky 30 | † |
| 10/23/2010 | Western Kentucky 54 @ UL Lafayette Ragin' Cajuns 21 | † |
| 10/30/2010 | North Texas Eagles 33 @ Western Kentucky 6 | † |
| 11/6/2010 | Florida Atlantic Owls 17 @ Western Kentucky 16 | † |
| 11/13/2010 | Western Kentucky 36 @ Arkansas State Red Wolves 35 1OT | † |
| 11/20/2010 | Middle Tenn State Blue Raiders 27 @ Western Kentucky 26 | † |
| 11/27/2010 | Western Kentucky 14 @ Troy Trojans 28 | † |