| 1 | Mon Nov 4 | vs Jackson St | W97-40 | 1-0 | 1.000 | #4 | ESPN+ | Fertitta Center · Houston, TX |
| 2 | Sat Nov 9 | vs#11Auburn | L69-74 | 1-1 | .500 | #4 | ESPNU | Fertitta Center · Houston, TX |
| 3 | Wed Nov 13 | vsLouisiana | W91-45 | 2-1 | .667 | #8 | ESPN+ | Fertitta Center · Houston, TX |
| 4 | Fri Nov 22 | vsHofstra | W80-44 | 3-1 | .750 | #7 | ESPN+ | Fertitta Center · Houston, TX |
| 5 | Tue Nov 26 | vs#9Alabama | L80-85 (OT) | 3-2 | .600 | #6 | TBS | Fertitta Center · Houston, TX |
| 6 | Thu Nov 28 | atNotre Dame | W65-54 | 4-2 | .667 | #6 | TBS | Purcell Pavilion · South Bend, IN |
| 7 | Sat Nov 30 | vsSDSU | L70-73 (OT) | 4-3 | .571 | #6 | TNT | Fertitta Center · Houston, TX |
| 8 | Sat Dec 7 | vsButler | W79-51 | 5-3 | .625 | #17 | ESPN2 | Fertitta Center · Houston, TX |
| 9 | Tue Dec 10 | vsTroy | W62-42 | 6-3 | .667 | #15 | ESPN+ | Fertitta Center · Houston, TX |
| 10 | Wed Dec 18 | vsToledo | W78-49 | 7-3 | .700 | #15 | ESPN+ | Fertitta Center · Houston, TX |
| 11 | Sat Dec 21 | vsTexas A&M-CC | W87-51 | 8-3 | .727 | #15 | CBS | Fertitta Center · Houston, TX |
| 12 | Mon Dec 30 | atOklahoma St | W60-47 | 9-3 | .750 | #14 | ESPN+ | Gallagher-Iba Arena · Stillwater, OK |
| 13 | Sat Jan 4 | vsBYU | W86-55 | 10-3 | .769 | #14 | ESPN+ | Fertitta Center · Houston, TX |
| 14 | Mon Jan 6 | vsTCU | W65-46 | 11-3 | .786 | #12 | ESPN2 | Fertitta Center · Houston, TX |
| 15 | Sat Jan 11 | atKansas St | W87-57 | 12-3 | .800 | #12 | ESPN+ | Bramlage Coliseum · Manhattan, KS |
| 16 | Wed Jan 15 | vsWest Virginia | W70-54 | 13-3 | .813 | #10 | ESPN+ | Fertitta Center · Houston, TX |
| 17 | Sat Jan 18 | atUCF | W69-68 | 14-3 | .824 | #10 | CBS | Addition Financial Arena · Orlando, FL |
| 18 | Wed Jan 22 | vsUtah | W70-36 | 15-3 | .833 | #7 | ESPN+ | Fertitta Center · Houston, TX |
| 19 | Sat Jan 25 | at#12Kansas | W92-86 (2OT) | 16-3 | .842 | #7 | ESPN | Allen Fieldhouse · Lawrence, KS |
| 20 | Wed Jan 29 | atWest Virginia | W63-49 | 17-3 | .850 | #6 | ESPN+ | WVU Coliseum · Morgantown, WV |
| 21 | Sat Feb 1 | vs#22Texas Tech | L81-82 (OT) | 17-4 | .810 | #6 | ESPN2 | Fertitta Center · Houston, TX |
| 22 | Tue Feb 4 | vsOklahoma St | W72-63 | 18-4 | .818 | #5 | ESPN+ | Fertitta Center · Houston, TX |
| 23 | Sat Feb 8 | atColorado | W69-59 | 19-4 | .826 | #5 | ESPN+ | CU Events Center · Boulder, CO |
| 24 | Mon Feb 10 | vsBaylor | W76-65 | 20-4 | .833 | #6 | ESPNU | Fertitta Center · Houston, TX |
| 25 | Sat Feb 15 | at#13Arizona | W62-58 | 21-4 | .840 | #6 | ESPN | McKale Center · Tucson, AZ |
| 26 | Tue Feb 18 | atArizona St | W80-65 | 22-4 | .846 | #5 | ESPN2 | Desert Financial Arena · Tempe, AZ |
| 27 | Sat Feb 22 | vs#8Iowa State | W68-59 | 23-4 | .852 | #5 | ESPN | Fertitta Center · Houston, TX |
| 28 | Mon Feb 24 | at#10Texas Tech | W69-61 | 24-4 | .857 | #4 | ESPN | United Supermarkets Arena · Lubbock, TX |
| 29 | Sat Mar 1 | vsCincinnati | W73-64 | 25-4 | .862 | #4 | CBS | Fertitta Center · Houston, TX |
| 30 | Mon Mar 3 | vsKansas | W65-59 | 26-4 | .867 | #3 | ESPN | Fertitta Center · Houston, TX |
| 31 | Sat Mar 8 | atBaylor | W65-61 | 27-4 | .871 | #3 | ESPN | Ferrell Center · Waco, TX |
| 32 | Thu Mar 13 | vsColorado | W77-68 | 28-4 | .875 | #2 | ESPN2 | Fertitta Center · Houston, TX |
| 33 | Fri Mar 14 | vs#17BYU | W74-54 | 29-4 | .879 | #2 | ESPN2 | Fertitta Center · Houston, TX |
| 34 | Sat Mar 15 | vsArizona | W72-64 | 30-4 | .882 | #2 | ESPN | Fertitta Center · Houston, TX |
| 35 | Thu Mar 20 | vs#16SIUE | W78-40 | 31-4 | .886 | #1 | TBS | Fertitta Center · Houston, TX |
| 36 | Sat Mar 22 | vs#8Gonzaga | W81-76 | 32-4 | .889 | #1 | TNT | Fertitta Center · Houston, TX |
| 37 | Fri Mar 28 | vs#4Purdue | W62-60 | 33-4 | .892 | #1 | TBS | Lucas Oil Stadium · Indianapolis, IN |
| 38 | Sun Mar 30 | vs#2Tennessee | W69-50 | 34-4 | .895 | #1 | CBS | Lucas Oil Stadium · Indianapolis, IN |
| 39 | Sat Apr 5 | at#1Duke | W70-67 | 35-4 | .897 | #1 | CBS | Alamodome · San Antonio, TX |
| 40 | Mon Apr 7 | vs#1Florida | L63-65 | 35-5 | .875 | #1 | CBS | Alamodome · San Antonio, TX |
