| 9/11/2010 | Rose-Hulman Engineers 16 @ DePauw 45 | |
| 9/18/2010 | DePauw 21 @ Centre Praying Colonels 16 | † |
| 9/25/2010 | Sewanee Tigers 7 @ DePauw 35 | † |
| 10/2/2010 | DePauw 35 @ Millsaps Majors 21 | † |
| 10/9/2010 | Rhodes Lynx 18 @ DePauw 42 | † |
| 10/16/2010 | Adrian Bulldogs 19 @ DePauw 23 | |
| 10/23/2010 | DePauw 32 @ Trinity TX Tigers 31 | † |
| 10/30/2010 | Birmingham-Southern Panthers 23 @ DePauw 30 | † |
| 11/6/2010 | Austin Kangaroos 20 @ DePauw 30 | † |
| 11/13/2010 | DePauw 0 @ Wabash Little Giants 47 | |
| 11/20/2010 | Trine Thunder 45 @ DePauw 35 (D3 Playoffs Round 1) |