| 1 | Wed Nov 6 | vs North Alabama | W77-55 | 1-0 | 1.000 | - | | Colonial Life Arena · Columbia, SC |
| 2 | Sun Nov 10 | vsWyoming | W66-32 | 2-0 | 1.000 | - | SEC Network | Colonial Life Arena · Columbia, SC |
| 3 | Fri Nov 15 | vsCleveland St | W90-63 | 3-0 | 1.000 | - | | Colonial Life Arena · Columbia, SC |
| 4 | Tue Nov 19 | vsBoston Univ | L70-78 | 3-1 | .750 | - | | Colonial Life Arena · Columbia, SC |
| 5 | Fri Nov 22 | vsGardner-Webb | W74-69 | 4-1 | .800 | - | | Colonial Life Arena · Columbia, SC |
| 6 | Tue Nov 26 | vsWichita St | L47-70 | 4-2 | .667 | - | CBSSN | Colonial Life Arena · Columbia, SC |
| 7 | Wed Nov 27 | atNorthern Iowa | L72-78 | 4-3 | .571 | - | CBSSN | McLeod Center · Cedar Falls, IA |
| 8 | Sun Dec 1 | vsG Washington | W74-65 | 5-3 | .625 | - | | Colonial Life Arena · Columbia, SC |
| 9 | Wed Dec 4 | atUMass | W84-80 | 6-3 | .667 | - | CBSSN | William D. Mullins Memorial Center · Amherst, MA |
| 10 | Sun Dec 8 | vsHouston | L56-76 | 6-4 | .600 | - | ESPNU | Colonial Life Arena · Columbia, SC |
| 11 | Sun Dec 15 | atClemson | W67-54 | 7-4 | .636 | - | ESPN2 | Littlejohn Coliseum · Clemson, SC |
| 12 | Sun Dec 22 | at9Virginia | W70-59 | 8-4 | .667 | - | ABC | John Paul Jones Arena · Charlottesville, VA |
| 13 | Mon Dec 30 | vsStetson | L56-63 | 8-5 | .615 | - | | Colonial Life Arena · Columbia, SC |
| 14 | Tue Jan 7 | vsFlorida | L68-81 | 8-6 | .571 | - | ESPNU | Colonial Life Arena · Columbia, SC |
| 15 | Sat Jan 11 | atTennessee | L55-56 | 8-7 | .533 | - | SEC Network | Thompson-Boling Arena · Knoxville, TN |
| 16 | Wed Jan 15 | vs10Kentucky | W81-78 | 9-7 | .563 | - | SEC Network | Colonial Life Arena · Columbia, SC |
| 17 | Sat Jan 18 | atTexas A&M | W81-67 | 10-7 | .588 | - | SEC Network | Reed Arena · College Station, TX |
| 18 | Wed Jan 22 | at16Auburn | L67-80 | 10-8 | .556 | - | ESPNU | Neville Arena · Auburn, AL |
| 19 | Sat Jan 25 | vsVanderbilt | W90-64 | 11-8 | .579 | - | SEC Network | Colonial Life Arena · Columbia, SC |
| 20 | Wed Jan 29 | atArkansas | W79-77 | 12-8 | .600 | - | SEC Network | Bud Walton Arena · Fayetteville, AR |
| 21 | Sat Feb 1 | vsMissouri | W76-54 | 13-8 | .619 | - | SEC Network | Colonial Life Arena · Columbia, SC |
| 22 | Wed Feb 5 | atOle Miss | L70-84 | 13-9 | .591 | - | SEC Network | SJB Pavilion · Oxford, MS |
| 23 | Sat Feb 8 | vsTexas A&M | W74-54 | 14-9 | .609 | - | SEC Network | Colonial Life Arena · Columbia, SC |
| 24 | Wed Feb 12 | atGeorgia | W75-59 | 15-9 | .625 | - | SEC Network | Stegeman Coliseum · Athens, GA |
| 25 | Sat Feb 15 | vsTennessee | W63-61 | 16-9 | .640 | - | SEC Network | Colonial Life Arena · Columbia, SC |
| 26 | Wed Feb 19 | atMississippi St | L76-79 | 16-10 | .615 | - | SEC Network | Humphrey Coliseum · Starkville, MS |
| 27 | Sat Feb 22 | vsLSU | L80-86 | 16-11 | .593 | - | ESPN2 | Colonial Life Arena · Columbia, SC |
| 28 | Wed Feb 26 | vsGeorgia | W94-90 (OT) | 17-11 | .607 | - | SEC Network | Colonial Life Arena · Columbia, SC |
| 29 | Sat Feb 29 | atAlabama | L86-90 | 17-12 | .586 | - | SEC Network | Coleman Coliseum · Tuscaloosa, AL |
| 30 | Tue Mar 3 | vsMississippi St | W83-71 | 18-12 | .600 | - | SEC Network | Colonial Life Arena · Columbia, SC |
| 31 | Sat Mar 7 | atVanderbilt | L74-83 | 18-13 | .581 | - | SEC Network | Memorial Gymnasium (TN) · Nashville, TN |
