| 1 | Mon Nov 6 | vs UMBC | W94-93 | 1-0 | 1.000 | - | | KFC Yum! Center · Louisville, KY |
| 2 | Fri Nov 10 | vs Chattanooga | L71-81 | 1-1 | .500 | - | | KFC Yum! Center · Louisville, KY |
| 3 | Wed Nov 15 | vs Coppin St | W61-41 | 2-1 | .667 | - | | KFC Yum! Center · Louisville, KY |
| 4 | Sun Nov 19 | vs #19Texas | L80-81 | 2-2 | .500 | - | ESPN | KFC Yum! Center · Louisville, KY |
| 5 | Mon Nov 20 | vs Indiana | L66-74 | 2-3 | .400 | - | ESPNU | KFC Yum! Center · Louisville, KY |
| 6 | Sun Nov 26 | vs New Mexico St | W90-84 (OT) | 3-3 | .500 | - | | KFC Yum! Center · Louisville, KY |
| 7 | Wed Nov 29 | vs Bellarmine | W73-68 | 4-3 | .571 | - | | KFC Yum! Center · Louisville, KY |
| 8 | Sun Dec 3 | at Virginia Tech | L68-75 | 4-4 | .500 | - | ACC Network | Cassell Coliseum · Blacksburg, VA |
| 9 | Sat Dec 9 | at DePaul | L68-75 | 4-5 | .444 | - | FS1 | Wintrust Arena · Chicago, IL |
| 10 | Wed Dec 13 | vs Arkansas St | L63-75 | 4-6 | .400 | - | ACC Network | KFC Yum! Center · Louisville, KY |
| 11 | Sun Dec 17 | vs Pepperdine | W85-63 | 5-6 | .455 | - | ACC Network | KFC Yum! Center · Louisville, KY |
| 12 | Thu Dec 21 | vs #9Kentucky | L76-95 | 5-7 | .417 | - | ESPN | KFC Yum! Center · Louisville, KY |
| 13 | Wed Jan 3 | at Virginia | L53-77 | 5-8 | .385 | - | ESPN2 | John Paul Jones Arena · Charlottesville, VA |
| 14 | Sat Jan 6 | vs Pitt | L70-83 | 5-9 | .357 | - | The CW Network | KFC Yum! Center · Louisville, KY |
| 15 | Wed Jan 10 | at Miami | W80-71 | 6-9 | .400 | - | ACC Network | Watsco Center · Coral Gables, FL |
| 16 | Sat Jan 13 | vs NC State | L83-89 | 6-10 | .375 | - | The CW Network | KFC Yum! Center · Louisville, KY |
| 17 | Wed Jan 17 | at #4UNC | L70-86 | 6-11 | .353 | - | ACC Network | Dean E. Smith Center · Chapel Hill, NC |
| 18 | Sat Jan 20 | at Wake Forest | L65-90 | 6-12 | .333 | - | ESPNU | Lawrence Joel Veterans Memorial Coliseum · Winston-Salem, NC |
| 19 | Tue Jan 23 | vs #12Duke | L69-83 | 6-13 | .316 | - | ACC Network | KFC Yum! Center · Louisville, KY |
| 20 | Sat Jan 27 | vsVirginia | L52-69 | 6-14 | .300 | - | The CW Network | KFC Yum! Center · Louisville, KY |
| 21 | Tue Jan 30 | at Clemson | L64-70 | 6-15 | .286 | - | ACC Network | Littlejohn Coliseum · Clemson, SC |
| 22 | Sat Feb 3 | vs Florida St | W101-92 | 7-15 | .318 | - | ACC Network | KFC Yum! Center · Louisville, KY |
| 23 | Wed Feb 7 | at Syracuse | L92-94 | 7-16 | .304 | - | ACC Network | JMA Wireless Dome · Syracuse, NY |
| 24 | Sat Feb 10 | vs Georgia Tech | W79-67 | 8-16 | .333 | - | ACC Network | KFC Yum! Center · Louisville, KY |
| 25 | Tue Feb 13 | at Boston College | L77-89 | 8-17 | .320 | - | ACC Network | Silvio O. Conte Forum · Chestnut Hill, MA |
| 26 | Sat Feb 17 | atPitt | L59-86 | 8-18 | .308 | - | ACC Network | Petersen Events Center · Pittsburgh, PA |
| 27 | Wed Feb 21 | vs Notre Dame | L50-72 | 8-19 | .296 | - | ESPNU | KFC Yum! Center · Louisville, KY |
| 28 | Wed Feb 28 | at#10Duke | L59-84 | 8-20 | .286 | - | ACC Network | Cameron Indoor Stadium · Durham, NC |
| 29 | Sat Mar 2 | vsSyracuse | L76-82 | 8-21 | .276 | - | ACC Network | KFC Yum! Center · Louisville, KY |
| 30 | Tue Mar 5 | vsVirginia Tech | L64-80 | 8-22 | .267 | - | ESPNU | KFC Yum! Center · Louisville, KY |
| 31 | Sat Mar 9 | vsBoston College | L61-67 | 8-23 | .258 | - | The CW Network | KFC Yum! Center · Louisville, KY |
| 32 | Tue Mar 12 | atNC State | L85-94 | 8-24 | .250 | - | ACC Network | PNC Arena · Raleigh, NC |
