The Fighting Irish limited the Wildcats to 19 field goals for the contest en route to their 41st victory in their last 42 home games.
Notre Dame advanced to 7-1, its lone loss having come against St. Joseph's in the third game of the season.
Kentucky held a one-point lead with 9:30 to play in the first half before Notre Dame went on a 19-7 run to end the period. The Fighting Irish advantage grew to 19 points midway through the second half.
Jerian Grant and Jack Cooley both had 13 points for Notre Dame.
Julius Mays scored 16 points for Kentucky (4-2). The Wildcats had won three in a row since losing to Duke Nov. 13.