| 1 | Mon Nov 3 | vs SC State | W104-45 | 1-0 | 1.000 | #11 | ACC Network | KFC Yum! Center · Louisville, KY |
| 2 | Thu Nov 6 | vsJackson St | W106-70 | 2-0 | 1.000 | #11 | ACC Extra | KFC Yum! Center · Louisville, KY |
| 3 | Tue Nov 11 | vs9Kentucky | W96-88 | 3-0 | 1.000 | #12 | ESPN | KFC Yum! Center · Louisville, KY |
| 4 | Sat Nov 15 | vsOhio | W106-81 | 4-0 | 1.000 | #12 | The CW Network | KFC Yum! Center · Louisville, KY |
| 5 | Fri Nov 21 | atCincinnati | W74-64 | 5-0 | 1.000 | #6 | ESPN2 | Fifth Third Arena · Cincinnati, OH |
| 6 | Mon Nov 24 | vsE Michigan | W87-46 | 6-0 | 1.000 | #6 | ACC Network | KFC Yum! Center · Louisville, KY |
| 7 | Wed Nov 26 | vsNJIT | W104-47 | 7-0 | 1.000 | #6 | ACC Network | KFC Yum! Center · Louisville, KY |
| 8 | Wed Dec 3 | at25Arkansas | L80-89 | 7-1 | .875 | #6 | ESPN | Bud Walton Arena · Fayetteville, AR |
| 9 | Sat Dec 6 | vs22Indiana | W87-78 | 8-1 | .889 | #6 | CBS | KFC Yum! Center · Louisville, KY |
| 10 | Sat Dec 13 | vsMemphis | W99-73 | 9-1 | .900 | #11 | ESPN | KFC Yum! Center · Louisville, KY |
| 11 | Tue Dec 16 | at20Tennessee | L62-83 | 9-2 | .818 | #11 | ESPN | Thompson-Boling Arena · Knoxville, TN |
| 12 | Sat Dec 20 | vsMontana | W94-54 | 10-2 | .833 | #11 | ACC Extra | KFC Yum! Center · Louisville, KY |
| 13 | Tue Dec 30 | atCalifornia | W90-70 | 11-2 | .846 | #16 | ACC Network | Haas Pavilion · Berkeley, CA |
| 14 | Fri Jan 2 | atStanford | L76-80 | 11-3 | .786 | #16 | ACC Network | Maples Pavilion · Stanford, CA |
| 15 | Tue Jan 6 | vs6Duke | L73-84 | 11-4 | .733 | #20 | ESPN | KFC Yum! Center · Louisville, KY |
| 16 | Sat Jan 10 | vsBoston College | W75-62 | 12-4 | .750 | #20 | The CW Network | KFC Yum! Center · Louisville, KY |
| 17 | Tue Jan 13 | vs16Virginia | L70-79 | 12-5 | .706 | #20 | ESPN2 | KFC Yum! Center · Louisville, KY |
| 18 | Sat Jan 17 | atPitt | W100-59 | 13-5 | .722 | #20 | ESPN2 | Petersen Events Center · Pittsburgh, PA |
| 19 | Sat Jan 24 | vsVirginia Tech | W85-71 | 14-5 | .737 | #23 | The CW Network | KFC Yum! Center · Louisville, KY |
| 20 | Mon Jan 26 | at4Duke | L52-83 | 14-6 | .700 | #20 | ESPN | Cameron Indoor Stadium · Durham, NC |
| 21 | Sat Jan 31 | vsSMU | W88-74 | 15-6 | .714 | #20 | ESPN | KFC Yum! Center · Louisville, KY |
| 22 | Wed Feb 4 | vsNotre Dame | W76-65 | 16-6 | .727 | #24 | ESPN2 | KFC Yum! Center · Louisville, KY |
| 23 | Sat Feb 7 | atWake Forest | W88-80 | 17-6 | .739 | #24 | ACC Network | Lawrence Joel Veterans Memorial Coliseum · Winston-Salem, NC |
| 24 | Mon Feb 9 | vsNC State | W118-77 | 18-6 | .750 | #24 | ESPN | KFC Yum! Center · Louisville, KY |
| 25 | Sat Feb 14 | atBaylor | W82-71 | 19-6 | .760 | #24 | ESPN | Ferrell Center · Waco, TX |
| 26 | Tue Feb 17 | atSMU | L85-95 | 19-7 | .731 | #21 | ESPN2 | Moody Coliseum · Dallas, TX |
| 27 | Sat Feb 21 | vsGeorgia Tech | W87-70 | 20-7 | .741 | #21 | The CW Network | KFC Yum! Center · Louisville, KY |
| 28 | Mon Feb 23 | at18UNC | L74-77 | 20-8 | .714 | #24 | ESPN | Dean E. Smith Center · Chapel Hill, NC |
| 29 | Sat Feb 28 | atClemson | L75-80 | 20-9 | .690 | #24 | ESPN2 | Littlejohn Coliseum · Clemson, SC |
