Schedule:
Please note: All rankings shown are the rankings of the teams on the date that they played one another
| Game | Date | Away Team (Rank) | Away Score | Home Score | Home Team (Rank) | Game Status | Result | Margin |
|---|---|---|---|---|---|---|---|---|
| 1 | 2021-10-17 | Rutgers (35) | 0 | 0 | Villanova (21) | Cancelled | - | - |
| 2 | 2021-11-09 | Mount St Mary's (179) | 51 | 91 | Villanova (21) | Final | W | 40 |
| 3 | 2021-11-12 | Villanova (29) | 77 | 86 | UCLA (30) | Final/OT | L | -9 |
| 4 | 2021-11-16 | Howard (103) | 81 | 100 | Villanova (123) | Final | W | 19 |
| 5 | 2021-11-20 | Villanova (29) | 71 | 53 | Tennessee (18) | Final | W | 18 |
| 6 | 2021-11-21 | Villanova (57) | 74 | 80 | Purdue (4) | Final | L | -6 |
| 7 | 2021-11-28 | Villanova (46) | 72 | 46 | La Salle (239) | Final | W | 26 |
| 8 | 2021-12-01 | Villanova (29) | 71 | 56 | Penn (131) | Final | W | 15 |
| 9 | 2021-12-04 | Saint Joseph's (99) | 52 | 81 | Villanova (29) | Final | W | 29 |
| 10 | 2021-12-07 | Villanova (29) | 67 | 53 | Syracuse (84) | Final | W | 14 |
| 11 | 2021-12-12 | Villanova (29) | 36 | 57 | Baylor (58) | Final | L | -21 |
| 12 | 2021-12-17 | Villanova (29) | 59 | 79 | Creighton (78) | Final | L | -20 |
| 13 | 2021-12-21 | Xavier (92) | 58 | 71 | Villanova (29) | Final | W | 13 |
| 14 | 2021-12-29 | Temple (169) | 0 | 0 | Villanova (29) | Cancelled | - | - |
| 15 | 2022-01-01 | Villanova (29) | 73 | 67 | Seton Hall (53) | Final | W | 6 |
| 16 | 2022-01-05 | Creighton (78) | 41 | 75 | Villanova (29) | Final | W | 34 |
| 17 | 2022-01-08 | Villanova (29) | 79 | 64 | DePaul (95) | Final | W | 15 |
| 18 | 2022-01-12 | Villanova (14) | 64 | 60 | Xavier (13) | Final | W | 4 |
| 19 | 2022-01-16 | Butler (111) | 42 | 82 | Villanova (11) | Final | W | 40 |
| 20 | 2022-01-19 | Marquette (106) | 57 | 54 | Villanova (29) | Final | L | -3 |
| 21 | 2022-01-22 | Villanova (29) | 85 | 74 | Georgetown (83) | Final | W | 11 |
| 22 | 2022-01-25 | DePaul (91) | 43 | 67 | Villanova (15) | Final | W | 24 |
| 23 | 2022-01-29 | St. John's (12) | 62 | 73 | Villanova (29) | Final | W | 11 |
| 24 | 2022-02-02 | Villanova (13) | 73 | 83 | Marquette (24) | Final | L | -10 |
| 25 | 2022-02-05 | Connecticut (4) | 74 | 85 | Villanova (29) | Final | W | 11 |
| 26 | 2022-02-08 | Villanova (13) | 75 | 69 | St. John's (76) | Final | W | 6 |
| 27 | 2022-02-12 | Seton Hall (53) | 67 | 73 | Villanova (29) | Final | W | 6 |
| 28 | 2022-02-15 | Villanova (9) | 89 | 84 | Providence (8) | Final | W | 5 |
| 29 | 2022-02-19 | Georgetown (204) | 66 | 74 | Villanova (9) | Final | W | 8 |
| 30 | 2022-02-22 | Villanova (9) | 69 | 71 | Connecticut (17) | Final | L | -2 |
| 31 | 2022-03-01 | Providence (7) | 74 | 76 | Villanova (14) | Final | W | 2 |
| 32 | 2022-03-05 | Villanova (14) | 78 | 59 | Butler (112) | Final | W | 19 |
| 33 | 2022-03-10 | St. John's (71) | 65 | 66 | Villanova (8) | Final | W | 1 |
| 34 | 2022-03-11 | Connecticut (18) | 60 | 63 | Villanova (8) | Final | W | 3 |
| 35 | 2022-03-12 | Creighton (40) | 48 | 54 | Villanova (8) | Final | W | 6 |
| 36 | 2022-03-18 | Delaware (121) | 60 | 80 | Villanova (7) | Final | W | 20 |
| 37 | 2022-03-20 | Ohio State (34) | 61 | 71 | Villanova (7) | Final | W | 10 |
| 38 | 2022-03-24 | Michigan (45) | 55 | 63 | Villanova (7) | Final | W | 8 |
| 39 | 2022-03-26 | Houston (9) | 44 | 50 | Villanova (7) | Final | W | 6 |
| 40 | 2022-04-02 | Villanova (7) | 65 | 81 | Kansas (3) | Final | L | -16 |