| 9/4/2010 | Nicholls State 0 @ San Diego State Aztecs 47 | |
| 9/11/2010 | Nicholls State 14 @ Western Michigan Broncos 49 | |
| 9/18/2010 | Nicholls State 21 @ South Alabama Jaguars 39 | |
| 9/25/2010 | Bacone Warriors 28 @ Nicholls State 44 | |
| 10/9/2010 | Sam Houston Bearkats 26 @ Nicholls State 7 | † |
| 10/16/2010 | Nicholls State 47 @ Texas State Bobcats 45 | † |
| 10/23/2010 | Central Arkansas Bears 31 @ Nicholls State 7 | † |
| 10/30/2010 | Nicholls State 14 @ McNeese State Cowboys 24 | † |
| 11/6/2010 | Stephen F. Austin Lumberjacks 48 @ Nicholls State 13 | † |
| 11/13/2010 | Nicholls State 37 @ Northwestern State Demons 7 | † |
| 11/18/2010 | Southeastern Louisiana Lions 25 @ Nicholls State 27 | † |