| 9/4/2010 | Defiance 13 @ Muskingum Muskies 19 2OT | |
| 9/11/2010 | Defiance 14 @ Adrian Bulldogs 40 | |
| 9/18/2010 | Defiance 24 @ Hanover Panthers 10 | † |
| 9/25/2010 | Franklin Grizzlies 42 @ Defiance 7 | † |
| 10/9/2010 | Mt St Joseph Lions 14 @ Defiance 22 | † |
| 10/16/2010 | Defiance 33 @ Earlham Hustlin' Quakers 0 | † |
| 10/23/2010 | Anderson Ravens 7 @ Defiance 49 | † |
| 10/30/2010 | Rose-Hulman Engineers 21 @ Defiance 41 | † |
| 11/6/2010 | Defiance 10 @ Manchester Spartans 7 | † |
| 11/13/2010 | Defiance 16 @ Bluffton Beavers 21 | † |