Kyle Wilter scored 26 points off the bench to lead the Wildcats (14-6, 5-2 SEC), who have won four of their last five games and beat a ranked opponent for the first time this season.
Wilter hit five 3-point shots and picked up seven rebounds. Alex Poythress scored 15 points and Nerlens Noel blocked a dozen shots and grabbed seven boards while scoring only two points.
LaDarius White led Ole Miss (17-3, 6-1) with 22 points and Marshall Henderson added 21. The Rebels had won nine consecutive games heading into Tuesday's contest.
Ole Miss led 38-37 at halftime but was undone by Kentucky's hot hand in the second half and an 0-8 streak midway through the half. The Rebels shot 32.9 percent from the field to 50 percent for Kentucky.