| 1 | Mon Nov 3 | at 8BYU | L66-71 | 0-1 | .000 | - | TNT | T-Mobile Arena · Las Vegas, NV |
| 2 | Sat Nov 8 | vsQueens | W94-74 | 1-1 | .500 | - | ESPN+ | Finneran Pavilion · Villanova, PA |
| 3 | Tue Nov 11 | vsSacred Heart | W94-60 | 2-1 | .667 | - | ESPN+ | Finneran Pavilion · Villanova, PA |
| 4 | Sat Nov 15 | vsDuquesne | W87-77 | 3-1 | .750 | - | truTV | Finneran Pavilion · Villanova, PA |
| 5 | Wed Nov 19 | atLa Salle | W70-55 | 4-1 | .800 | - | CBSSN | Tom Gola Arena · Philadelphia, PA |
| 6 | Tue Nov 25 | vsOld Dominion | W89-75 | 5-1 | .833 | - | ESPN+ | Finneran Pavilion · Villanova, PA |
| 7 | Mon Dec 1 | vsTemple | W74-56 | 6-1 | .857 | - | FS1 | Finneran Pavilion · Villanova, PA |
| 8 | Sat Dec 6 | vsPenn | W90-63 | 7-1 | .875 | - | | Xfinity Mobile Arena · Philadelphia, PA |
| 9 | Tue Dec 9 | at2Michigan | L61-89 | 7-2 | .778 | - | FS1 | Crisler Center · Ann Arbor, MI |
| 10 | Sat Dec 13 | vsPitt | W79-61 | 8-2 | .800 | - | truTV | Finneran Pavilion · Villanova, PA |
| 11 | Fri Dec 19 | vsWisconsin | W76-66 (OT) | 9-2 | .818 | - | FOX | Fiserv Forum · Milwaukee, WI |
| 12 | Tue Dec 23 | atSeton Hall | W64-56 | 10-2 | .833 | - | Peacock | Prudential Center · Newark, NJ |
| 13 | Wed Dec 31 | vsDePaul | W71-66 | 11-2 | .846 | - | FS1 | Finneran Pavilion · Villanova, PA |
| 14 | Sat Jan 3 | atButler | W85-67 | 12-2 | .857 | - | TNT | Hinkle Fieldhouse · Indianapolis, IN |
| 15 | Wed Jan 7 | vsCreighton | L72-76 | 12-3 | .800 | - | Peacock | Finneran Pavilion · Villanova, PA |
| 16 | Sat Jan 10 | atMarquette | W76-73 | 13-3 | .813 | - | TNT | Fiserv Forum · Milwaukee, WI |
| 17 | Tue Jan 13 | atProvidence | W88-82 | 14-3 | .824 | - | FS1 | Amica Mutual Pavilion · Providence, RI |
| 18 | Sat Jan 17 | vsSt John's | L79-86 | 14-4 | .778 | - | Peacock | Xfinity Mobile Arena · Philadelphia, PA |
| 19 | Wed Jan 21 | vsGeorgetown | W66-51 | 15-4 | .789 | - | Peacock | Finneran Pavilion · Villanova, PA |
| 20 | Sat Jan 24 | at2UConn | L67-75 (OT) | 15-5 | .750 | - | FOX | Gampel Pavilion · Storrs, CT |
| 21 | Fri Jan 30 | vsProvidence | W87-73 | 16-5 | .762 | - | FS1 | Finneran Pavilion · Villanova, PA |
| 22 | Wed Feb 4 | vsSeton Hall | W72-60 | 17-5 | .773 | - | Peacock | Finneran Pavilion · Villanova, PA |
| 23 | Sat Feb 7 | atGeorgetown | W80-73 | 18-5 | .783 | - | TNT | Capital One Arena · Washington, D.C. |
| 24 | Tue Feb 10 | vsMarquette | W77-74 | 19-5 | .792 | - | TNT | Finneran Pavilion · Villanova, PA |
| 25 | Sat Feb 14 | atCreighton | W80-69 | 20-5 | .800 | - | FOX | CHI Health Center Omaha · Omaha, NE |
| 26 | Tue Feb 17 | atXavier | W92-89 (OT) | 21-5 | .808 | - | FS1 | Cintas Center · Cincinnati, OH |
| 27 | Sat Feb 21 | vs5UConn | L63-73 | 21-6 | .778 | - | TNT | Xfinity Mobile Arena · Philadelphia, PA |
| 28 | Wed Feb 25 | vsButler | W82-73 | 22-6 | .786 | - | FS1 | Finneran Pavilion · Villanova, PA |
| 29 | Sat Feb 28 | at15St John's | L57-89 | 22-7 | .759 | - | FOX | Carnesecca Arena · Queens, NY |
| 30 | Wed Mar 4 | atDePaul | W76-57 | 23-7 | .767 | - | Peacock | Wintrust Arena · Chicago, IL |
| 31 | Sat Mar 7 | vsXavier | W91-78 | 24-7 | .774 | - | TNT | Finneran Pavilion · Villanova, PA |
| 32 | Thu Mar 12 | vsGeorgetown | L64-78 | 24-8 | .750 | - | FS1 | Finneran Pavilion · Villanova, PA |
| R1 | Fri Mar 20 | vs9Utah State | L76-86 | 24-9 | .727 | #8 | TNT | Viejas Arena · San Diego, CA |
