Schedule:
| Game | Date | Away Team (Rank) | Away Score | Home Team (Rank) | Home Score | Game Status | Result | Margin |
|---|---|---|---|---|---|---|---|---|
| 1 | 2021-09-04 | Holy Cross | 38 | Connecticut | 28 | Final | W | 10 |
| 2 | 2021-09-11 | Merrimack | 35 | Holy Cross | 21 | Final | L | -14 |
| 3 | 2021-09-18 | Holy Cross | 20 | Yale | 17 | Final | W | 3 |
| 4 | 2021-09-25 | Holy Cross | 45 | Monmouth | 15 | Final | W | 30 |
| 5 | 2021-10-02 | Harvard | 38 | Holy Cross | 13 | Final | L | -25 |
| 6 | 2021-10-16 | Georgetown | 14 | Holy Cross | 48 | Final | W | 34 |
| 7 | 2021-10-23 | Colgate | 10 | Holy Cross | 42 | Final | W | 32 |
| 8 | 2021-10-30 | Holy Cross | 31 | Lehigh | 12 | Final | W | 19 |
| 9 | 2021-11-06 | Lafayette | 10 | Holy Cross | 35 | Final | W | 25 |
| 10 | 2021-11-13 | Holy Cross | 52 | Fordham | 24 | Final | W | 28 |
| 11 | 2021-11-20 | Holy Cross | 45 | Bucknell | 6 | Final | W | 39 |
| 12 | 2021-11-27 | Sacred Heart (191) | 10 | Holy Cross (131) | 13 | Final | W | 3 |
| 13 | 2021-12-03 | Holy Cross (137) | 16 | Villanova (107) | 21 | Final | L | -5 |