| 1 | Wed Nov 25 | at Boston College | W76-67 | 1-0 | 1.000 | - | ESPN | Silvio O. Conte Forum · Chestnut Hill, MA |
| 2 | Thu Nov 26 | atArizona St | W83-74 | 2-0 | 1.000 | - | ESPN | Desert Financial Arena · Tempe, AZ |
| 3 | Sat Nov 28 | vsVirginia Tech | L73-81 (OT) | 2-1 | .667 | - | ESPNU | Finneran Pavilion · Villanova, PA |
| 4 | Tue Dec 1 | atTBD | W87-53 | 3-1 | .750 | - | ESPN2 | Mohegan Sun Arena |
| 5 | Wed Dec 2 | vsSaint Joseph's | PPD | 18-7 | .720 | #12 | FS1 | Finneran Pavilion · Villanova, PA |
| 7 | Sun Dec 6 | atTexas | W68-64 | 4-1 | .800 | - | ESPN | Moody Center · Austin, TX |
| 8 | Fri Dec 11 | atGeorgetown | W76-63 | 5-1 | .833 | #9 | FS1 | Capital One Arena · Washington, D.C. |
| 9 | Mon Dec 14 | vsDePaul | PPD | 18-7 | .720 | #7 | FS1 | Finneran Pavilion · Villanova, PA |
| 10 | Wed Dec 16 | vsButler | W85-66 | 6-1 | .857 | #7 | FS1 | Finneran Pavilion · Villanova, PA |
| 11 | Sat Dec 19 | vsSaint Joseph's | W88-68 | 7-1 | .875 | #7 | FS1 | Finneran Pavilion · Villanova, PA |
| 12 | Wed Dec 23 | atMarquette | W85-68 | 8-1 | .889 | #5 | FS1 | Fiserv Forum · Milwaukee, WI |
| 13 | Wed Dec 30 | vsSt John's | PPD | 18-7 | .720 | #4 | | Finneran Pavilion · Villanova, PA |
| 16 | Fri Jan 8 | vsMarquette | PPD | 18-7 | .720 | #3 | FS1 | Finneran Pavilion · Villanova, PA |
| 19 | Tue Jan 19 | vsSeton Hall | W76-74 | 9-1 | .900 | #3 | FS1 | Finneran Pavilion · Villanova, PA |
| 20 | Sat Jan 23 | vsProvidence | W71-56 | 10-1 | .909 | #3 | FOX | Finneran Pavilion · Villanova, PA |
| 22 | Sat Jan 30 | atSeton Hall | W80-72 | 11-1 | .917 | #3 | FOX | Prudential Center · Newark, NJ |
| 23 | Wed Feb 3 | atSt John's | L59-70 | 11-2 | .846 | #3 | CBSSN | Carnesecca Arena · Queens, NY |
| 24 | Sun Feb 7 | vsGeorgetown | W84-74 | 12-2 | .857 | #3 | | Finneran Pavilion · Villanova, PA |
| 26 | Wed Feb 10 | vsMarquette | W96-64 | 13-2 | .867 | #5 | FS1 | Finneran Pavilion · Villanova, PA |
| 27 | Sat Feb 13 | at19Creighton | L70-86 | 13-3 | .813 | #5 | FOX | CHI Health Center Omaha · Omaha, NE |
| 28 | Sat Feb 20 | vsUConn | W68-60 | 14-3 | .824 | #10 | FOX | Finneran Pavilion · Villanova, PA |
| 29 | Tue Feb 23 | vsSt John's | W81-58 | 15-3 | .833 | #8 | CBSSN | Finneran Pavilion · Villanova, PA |
| 30 | Sun Feb 28 | atButler | L61-73 | 15-4 | .789 | #8 | CBS | Hinkle Fieldhouse · Indianapolis, IN |
| 31 | Wed Mar 3 | vs14Creighton | W72-60 | 16-4 | .800 | #10 | FS1 | Finneran Pavilion · Villanova, PA |
| 32 | Sat Mar 6 | atProvidence | L52-54 | 16-5 | .762 | #10 | FOX | Amica Mutual Pavilion · Providence, RI |
| 33 | Thu Mar 11 | vsGeorgetown | L71-72 | 16-6 | .727 | - | FS1 | Finneran Pavilion · Villanova, PA |
| 27 | Fri Mar 19 | vs12Winthrop | W73-63 | 17-6 | .739 | #5 | TNT | Indiana Farmers Coliseum · Indianapolis, IN |
| 28 | Sun Mar 21 | vs13North Texas | W84-61 | 18-6 | .750 | #5 | TNT | Finneran Pavilion · Villanova, PA |
| 29 | Sat Mar 27 | at1Baylor | L51-62 | 18-7 | .720 | #5 | CBS | Hinkle Fieldhouse · Indianapolis, IN |
