| 9/4/2021 | Holy Cross | 38 | at | Connecticut (1-11) | 28 | at Ind | ||
| 9/11/2021 | Merrimack (5-6) | 35 | at | Holy Cross | 21 | NE | ||
| 9/18/2021 | Holy Cross | 20 | at | Yale (5-5) | 17 | at Ivy | ||
| 9/25/2021 | Holy Cross | 45 | at | Monmouth NJ (7-4) | 15 | at BigS | ||
| 10/2/2021 | Harvard (8-2) | 38 | at | Holy Cross | 13 | Ivy | ||
| 10/16/2021 | Georgetown (2-8,1-5) | 14 | at | Holy Cross | 48 | |||
| 10/23/2021 | Colgate (5-6,5-1) | 10 | at | Holy Cross | 42 | |||
| 10/30/2021 | Holy Cross | 31 | at | Lehigh (3-8,3-3) | 12 | |||
| 11/6/2021 | Lafayette (3-8,2-4) | 10 | at | Holy Cross | 35 | |||
| 11/13/2021 | Holy Cross | 52 | at | Fordham (6-5,4-2) | 24 | |||
| 11/20/2021 | Holy Cross | 45 | at | Bucknell (1-10,0-6) | 6 | |||
| 11/27/2021 | Sacred Heart (8-4) | 10 | at | Holy Cross | 13 | NE | ||
| 12/3/2021 | Holy Cross | 16 | at | Villanova (10-3) | 21 | at CAAF |
| vs Holy Cross | vs Other Opponents | Holy Cross compared to OOs | |
| Record: | 3-10 | 61-70 | |
| Points Scored: | 18.46 | 23.17 | 4.71 |
| Points Allowed: | 32.23 | 25.44 | 6.79 |
| Margin: | -13.77 | -2.27 | 11.50 |
| Total Points: | 50.69 | 48.61 | 2.08 |