Shekinna Stricklen posted a double-double with 22 points and 12 rebounds. Cierra Burdick was the Lady Vols' other double-figure scorer as she tallied 10.
Tennessee (19-7, 10-3) limited Mississippi State (14-12, 4-9) to just 13 points in the first half and a paltry 23.5 field goal percentage.
Kendra Grant led MSU with 17 and Porsha Grant tallied 15.
After scoring just two points in the first half, Stricklen racked up 20 of the Lady Vols 35 points in the second half.
Glory Johnson added seven points and a game-high 14 rebounds.
The Lady Vols took a 38-20 lead on a 3-pointer by Stricklen with 11:31 left in the game. Stricklen them moved the margin to 20 at 44-24 with a free throw with 8:26 left in the second half.
Down 20, the Bulldogs made a run to cut the deficit to 10 at 48-38 on a 3-point play by Porsha Porter with 3:38 left.
The game got off to a sluggish start as Tennessee led 2-0 with 14:26 left in the first half. The Lady Vols build a halftime lead of 22-13 and expanded the lead early in the second half.
The Lady Vols continue their two-game swing in Mississippi, travelling to Ole Miss for a Sunday game at 2 p.m. ET. The game airs on the SEC Network and can be heard on the Lady Vol Network.