| 9/4/2010 | Stony Brook Seawolves 14 @ South Florida 59 | |
| 9/11/2010 | South Florida 14 @ Florida Gators 38 | |
| 9/25/2010 | Western Kentucky Hilltoppers 12 @ South Florida 24 | |
| 10/2/2010 | Florida Atlantic Owls 3 @ South Florida 21 | |
| 10/9/2010 | Syracuse Orangemen 13 @ South Florida 9 | † |
| 10/14/2010 | South Florida 6 @ West Virginia Mountaineers 20 | † |
| 10/22/2010 | South Florida 38 @ Cincinnati Bearcats 30 | † |
| 11/3/2010 | Rutgers Scarlet Knights 27 @ South Florida 28 | † |
| 11/13/2010 | South Florida 24 @ Louisville Cardinals 21 1OT | † |
| 11/20/2010 | Pittsburgh Panthers 17 @ South Florida 10 | † |
| 11/27/2010 | South Florida 23 @ Miami-Florida Hurricanes 20 1OT | |
| 12/4/2010 | Connecticut Huskies 19 @ South Florida 16 | † |
| 12/31/2010 | South Florida 31 vs Clemson Tigers 26 (Charlotte - Meineke Bowl) |