The Wildcats (11-0) tied a school record with their 11th consecutive victory to open the season.
East Tennessee State (2-6) forced four lead changes and three ties in the first eight minutes, but the Wildcats used a 14-2 run to go up 31-18 with 8:15 remaining in the first half.
Kentucky led 49-29 at the half, but the Buccaneers pulled within 54-44 with 13:28 left. But East Tennessee State couldn't get within single digits.
Linnae Harper added 10 points for Kentucky.
Maria Bond led East Tennessee State with 14 points, and Chandler Christopher scored 11.