Chris Perez scored 16 points and Willie Green added 11 points and nine boards to help Stetson (10-13, 7-5) snap a three-game skid.
Trailing 65-54 with less than 6 minutes to play, Torrey Craig made consecutive 3-pointers for SC Upstate to cut the lead to five, 65-60 with 4:12 remaining.
After Perez’s 3-pointer pushed the lead to 68-60 with 3:04 left to play, Jodd Maxey converted a layup a minute later to cut the Spartans’ deficit to six, 68-62.
SC Upstate (13-12, 7-5) managed just two field goals in the final two minutes while Perez converted five free throws in the same span to ensure the victory.
Craig went 6 of 21 from the field and led the Spartans with 16 points.