| 1 | Tue Nov 9 | vs Mount St Mary | W91-51 | 1-0 | 1.000 | #4 | | Finneran Pavilion · Villanova, PA |
| 2 | Fri Nov 12 | at2UCLA | L77-86 (OT) | 1-1 | .500 | #4 | | Pauley Pavilion · Los Angeles, CA |
| 3 | Tue Nov 16 | vsHoward | W100-81 | 2-1 | .667 | #5 | | Finneran Pavilion · Villanova, PA |
| 4 | Sat Nov 20 | atTennessee | W71-53 | 3-1 | .750 | - | | Thompson-Boling Arena · Knoxville, TN |
| 5 | Sun Nov 21 | atPurdue | L74-80 | 3-2 | .600 | - | | Mackey Arena · West Lafayette, IN |
| 6 | Sun Nov 28 | atLa Salle | W72-46 | 4-2 | .667 | #7 | | The Palestra · Philadelphia, PA |
| 7 | Wed Dec 1 | atPenn | W71-56 | 5-2 | .714 | #6 | | The Palestra · Philadelphia, PA |
| 8 | Sat Dec 4 | vsSaint Joseph's | W81-52 | 6-2 | .750 | #6 | | Finneran Pavilion · Villanova, PA |
| 9 | Tue Dec 7 | atSyracuse | W67-53 | 7-2 | .778 | - | | JMA Wireless Dome · Syracuse, NY |
| 10 | Sun Dec 12 | atBaylor | L36-57 | 7-3 | .700 | - | | Ferrell Center · Waco, TX |
| 11 | Fri Dec 17 | atCreighton | L59-79 | 7-4 | .636 | #9 | | CHI Health Center Omaha · Omaha, NE |
| 12 | Tue Dec 21 | vs18Xavier | W71-58 | 8-4 | .667 | #23 | | Finneran Pavilion · Villanova, PA |
| 14 | Sat Jan 1 | at15Seton Hall | W73-67 | 9-4 | .692 | #22 | | Prudential Center · Newark, NJ |
| 15 | Wed Jan 5 | vsCreighton | W75-41 | 10-4 | .714 | #19 | | Finneran Pavilion · Villanova, PA |
| 16 | Sat Jan 8 | atDePaul | W79-64 | 11-4 | .733 | #19 | | Wintrust Arena · Chicago, IL |
| 17 | Wed Jan 12 | at17Xavier | W64-60 | 12-4 | .750 | #14 | | Cintas Center · Cincinnati, OH |
| 18 | Sun Jan 16 | vsButler | W82-42 | 13-4 | .765 | #14 | | Xfinity Mobile Arena · Philadelphia, PA |
| 19 | Wed Jan 19 | vsMarquette | L54-57 | 13-5 | .722 | #11 | | Finneran Pavilion · Villanova, PA |
| 20 | Sat Jan 22 | atGeorgetown | W85-74 | 14-5 | .737 | #11 | | Capital One Arena · Washington, D.C. |
| 21 | Tue Jan 25 | vsDePaul | W67-43 | 15-5 | .750 | #14 | | Finneran Pavilion · Villanova, PA |
| 22 | Sat Jan 29 | vsSt John's | W73-62 | 16-5 | .762 | #14 | | Finneran Pavilion · Villanova, PA |
| 23 | Wed Feb 2 | at24Marquette | L73-83 | 16-6 | .727 | #12 | | Fiserv Forum · Milwaukee, WI |
| 24 | Sat Feb 5 | vs17UConn | W85-74 | 17-6 | .739 | #12 | | Xfinity Mobile Arena · Philadelphia, PA |
| 25 | Tue Feb 8 | atSt John's | W75-69 | 18-6 | .750 | - | | Carnesecca Arena · Queens, NY |
| 26 | Sat Feb 12 | vsSeton Hall | W73-67 | 19-6 | .760 | #15 | | Xfinity Mobile Arena · Philadelphia, PA |
| 27 | Tue Feb 15 | at8Providence | W89-84 | 20-6 | .769 | #10 | | Amica Mutual Pavilion · Providence, RI |
| 28 | Sat Feb 19 | vsGeorgetown | W74-66 | 21-6 | .778 | #10 | | Finneran Pavilion · Villanova, PA |
| 29 | Tue Feb 22 | at21UConn | L69-71 | 21-7 | .750 | #8 | | Gampel Pavilion · Storrs, CT |
| 30 | Tue Mar 1 | vs9Providence | W76-74 | 22-7 | .759 | #11 | | Finneran Pavilion · Villanova, PA |
| 31 | Sat Mar 5 | atButler | W78-59 | 23-7 | .767 | #11 | | Hinkle Fieldhouse · Indianapolis, IN |
| 32 | Thu Mar 10 | vsSt John's | W66-65 | 24-7 | .774 | - | | Finneran Pavilion · Villanova, PA |
| 33 | Fri Mar 11 | vsUConn | W63-60 | 25-7 | .781 | - | | Finneran Pavilion · Villanova, PA |
| 34 | Sat Mar 12 | vsCreighton | W54-48 | 26-7 | .788 | - | | Finneran Pavilion · Villanova, PA |
| 34 | Fri Mar 18 | vs15Delaware | W80-60 | 27-7 | .794 | #2 | | Finneran Pavilion · Villanova, PA |
| 35 | Sun Mar 20 | vs7Ohio State | W71-61 | 28-7 | .800 | #2 | | Finneran Pavilion · Villanova, PA |
| 36 | Thu Mar 24 | vs11Michigan | W63-55 | 29-7 | .806 | #2 | | Finneran Pavilion · Villanova, PA |
| 37 | Sat Mar 26 | vs5Houston | W50-44 | 30-7 | .811 | #2 | | Finneran Pavilion · Villanova, PA |
| 38 | Sat Apr 2 | at1Kansas | L65-81 | 30-8 | .789 | #2 | | Caesars Superdome · New Orleans, LA |
