| 9/4/2010 | Howard Bison 7 @ Holy Cross 38 | |
| 9/11/2010 | Holy Cross 7 @ Massachusetts Minutemen 31 | |
| 9/18/2010 | Holy Cross 6 @ Harvard Crimson 34 | |
| 9/25/2010 | Holy Cross 7 @ Georgetown Hoyas 17 | † |
| 10/2/2010 | Fordham Rams 31 @ Holy Cross 36 | † |
| 10/9/2010 | Brown Bears 13 @ Holy Cross 17 | |
| 10/16/2010 | Holy Cross 19 @ Dartmouth Corsairs 27 | |
| 10/23/2010 | Holy Cross 31 @ Colgate Red Raiders 24 | † |
| 11/6/2010 | Lehigh Mountain Hawks 34 @ Holy Cross 17 | † |
| 11/13/2010 | Holy Cross 37 @ Lafayette Leopards 27 | † |
| 11/20/2010 | Bucknell Bison 9 @ Holy Cross 34 | † |