| 1 | Wed Nov 25 | vs Liberty | W77-64 | 1-0 | 1.000 | - | CBSSN | Mackey Arena · West Lafayette, IN |
| 2 | Thu Nov 26 | atClemson | L70-81 | 1-1 | .500 | - | CBSSN | Littlejohn Coliseum · Clemson, SC |
| 3 | Tue Dec 1 | vsOakland | W93-50 | 2-1 | .667 | - | BTN | Mackey Arena · West Lafayette, IN |
| 4 | Fri Dec 4 | vsValparaiso | W68-61 | 3-1 | .750 | - | BTN | Mackey Arena · West Lafayette, IN |
| 5 | Tue Dec 8 | atMiami | L54-58 | 3-2 | .600 | - | ESPN2 | Watsco Center · Coral Gables, FL |
| 6 | Sat Dec 12 | vsIndiana St | W80-68 | 4-2 | .667 | - | BTN | Mackey Arena · West Lafayette, IN |
| 7 | Wed Dec 16 | vs20Ohio State | W67-60 | 5-2 | .714 | - | BTN | Mackey Arena · West Lafayette, IN |
| 8 | Sat Dec 19 | vsNotre Dame | W88-78 | 6-2 | .750 | - | ESPN2 | Mackey Arena · West Lafayette, IN |
| 9 | Tue Dec 22 | at4Iowa | L55-70 | 6-3 | .667 | - | BTN | Carver-Hawkeye Arena · Iowa City, IA |
| 10 | Fri Dec 25 | vsMaryland | W73-70 | 7-3 | .700 | - | FS1 | Mackey Arena · West Lafayette, IN |
| 11 | Tue Dec 29 | at14Rutgers | L76-81 | 7-4 | .636 | - | FS1 | Jersey Mike’s Arena · Piscataway, NJ |
| 12 | Sat Jan 2 | at15Illinois | L58-66 | 7-5 | .583 | - | BTN | State Farm Center · Champaign, IL |
| 14 | Fri Jan 8 | at23Michigan St | W55-54 | 8-5 | .615 | - | FS1 | Breslin Center · East Lansing, MI |
| 15 | Thu Jan 14 | atIndiana | W81-69 | 9-5 | .643 | - | | Simon Skjodt Assembly Hall · Bloomington, IN |
| 16 | Sun Jan 17 | vsPenn State | W80-72 | 10-5 | .667 | - | | Mackey Arena · West Lafayette, IN |
| 17 | Tue Jan 19 | at15Ohio State | W67-65 | 11-5 | .688 | - | BTN | Value City Arena · Columbus, OH |
| 18 | Fri Jan 22 | vs7Michigan | L53-70 | 11-6 | .647 | - | FS1 | Mackey Arena · West Lafayette, IN |
| 19 | Sat Jan 30 | vs21Minnesota | W81-62 | 12-6 | .667 | - | BTN | Mackey Arena · West Lafayette, IN |
| 20 | Tue Feb 2 | atMaryland | L60-61 | 12-7 | .632 | #24 | BTN | XFINITY Center · College Park, MD |
| 21 | Sat Feb 6 | vsNorthwestern | W75-70 | 13-7 | .650 | #24 | | Mackey Arena · West Lafayette, IN |
| 22 | Thu Feb 11 | atMinnesota | L68-71 | 13-8 | .619 | #24 | ESPN2 | Williams Arena · Minneapolis, MN |
| 23 | Tue Feb 16 | vsMichigan St | W75-65 | 14-8 | .636 | - | ESPN | Mackey Arena · West Lafayette, IN |
| 24 | Sat Feb 20 | atNebraska | W75-58 | 15-8 | .652 | - | BTN | Pinnacle Bank Arena · Lincoln, NE |
| 25 | Fri Feb 26 | atPenn State | W73-52 | 16-8 | .667 | - | FS1 | Bryce Jordan Center · University Park, PA |
| 26 | Tue Mar 2 | vs25Wisconsin | W73-69 | 17-8 | .680 | #23 | ESPN2 | Mackey Arena · West Lafayette, IN |
| 27 | Sat Mar 6 | vsIndiana | W67-58 | 18-8 | .692 | #23 | ESPN | Mackey Arena · West Lafayette, IN |
| 28 | Fri Mar 12 | vsOhio State | L78-87 (OT) | 18-9 | .667 | - | BTN | Lucas Oil Stadium · Indianapolis, IN |
| 28 | Fri Mar 19 | vs13North Texas | L69-78 (OT) | 18-10 | .643 | #4 | TNT | Lucas Oil Stadium · Indianapolis, IN |
