| 9/2/2010 | Southern Miss 13 @ South Carolina Gamecocks 41 | |
| 9/11/2010 | Prairie View Panthers 7 @ Southern Miss 34 | |
| 9/17/2010 | Kansas Jayhawks 16 @ Southern Miss 31 | |
| 9/25/2010 | Southern Miss 13 @ Louisiana Tech Bulldogs 12 | |
| 10/2/2010 | Marshall Thundering Herd 16 @ Southern Miss 41 | † |
| 10/9/2010 | East Carolina Pirates 44 @ Southern Miss 43 | † |
| 10/16/2010 | Southern Miss 41 @ Memphis Tigers 19 | † |
| 10/30/2010 | UAB Blazers 50 @ Southern Miss 49 2OT | † |
| 11/6/2010 | Southern Miss 46 @ Tulane Green Wave 30 | † |
| 11/13/2010 | Southern Miss 31 @ UCF Knights 21 | † |
| 11/20/2010 | Houston Cougars 41 @ Southern Miss 59 | † |
| 11/26/2010 | Southern Miss 50 @ Tulsa Golden Hurricane 56 | † |
| 12/21/2010 | Southern Miss 28 vs Louisville Cardinals 31 (St Petersburg - Beef O'Brady's Bowl) |