Four Lady Vols scored in double-figures led Glory Johnson, who netted 13 points and grabbed eight rebounds. Shekinna Stricklen scored 12 points as both she and Johnson made 5-of-9 shots from the floor.
Vicki Baugh and Cierra Burdick each tallied 10 off the bench.
Tennessee improved to 20-7 overall and 11-3 in the SEC. Ole Miss fell to 12-15 overall and 2-12 in the league.
Valencia McFarland led the Rebels with 21 points, the only double-figure scorer for Ole Miss.
Tennessee took control of the game midway through the first half and held off the pesky Rebels. Down 15-14 with 9:37 left in the first half, a Stricklen layup with 9:10 left in the half and the Lady Vols never trailed again.
The Lady Vols led by as many as 12 points with 5:07 left in the second half on a free throw by Meighan Simmons, which made it 58-46. Ole Miss had trimmed the margin to four points at 50-46 on a 3-pointer by Amber Singletary with 8:28 left in regulation.
Tennessee shot 43.6 from the floor and limited Ole Miss to 37.3 while outrebounding the Rebels, 37-32.
Tennessee led 32-21 at halftime.
The Lady Vols return home to host Arkansas on Thursday at 7 p.m. The game airs on Fox Sports South and can be heard on the Lady Vol Network.
UT closes the regular-season vs. Florida on Sunday, Feb. 26, in a game that airs on ESPNU with a 3:30 p.m., tipoff.