| 9/4/2010 | Humboldt State Lumberjacks 17 @ Cal Poly 23 | |
| 9/11/2010 | Montana Grizzlies 33 @ Cal Poly 35 | |
| 9/18/2010 | Cal Poly 12 @ Texas State Bobcats 21 | |
| 9/25/2010 | Cal Poly 40 @ McNeese State Cowboys 14 | |
| 10/2/2010 | Cal Poly 17 @ Fresno State Bulldogs 38 | |
| 10/9/2010 | Cal Poly 50 @ Old Dominion Monarchs 37 | |
| 10/16/2010 | Cal Poly 7 @ Southern Utah Thunderbirds 20 | † |
| 10/23/2010 | North Dakota Sioux 21 @ Cal Poly 22 | † |
| 10/30/2010 | St Francis PA Fighting Saints 33 @ Cal Poly 41 | |
| 11/6/2010 | Cal Poly 38 @ South Dakota Coyotes 24 | † |
| 11/13/2010 | UC Davis Aggies 22 @ Cal Poly 21 | † |