Aaron Harrison added 14 points and Andrew Harrison 10 and Kentucky (12-3, 2-0) started off a two-game road swing through the Southeastern Conference with a win. Julius Randle had 10 of his 11 rebounds in the first half.
Kentucky coach John Calipari has nine freshmen, the same number of total players Vanderbilt coach Kevin Stallings has available right now with leading scorer Eric McClellan first suspended from the university Wednesday before being dismissed from the program on Friday.
That left senior Rod Odom as Vandy's leading scorer averaging 13.8 points a game, and he spent 10 minutes of the first half on the bench because of foul trouble. He finished with five points.
Freshman Damian Jones had a game-high 18 points and 11 rebounds for Vanderbilt. Kyle Fuller had 17 points and 10 assists, and Dai-Jon Parker added 17.
Vanderbilt outshot Kentucky 50 percent (25 of 50) to 42.6 percent (26 of 61 ).
But the Wildcats used their size for a 41-28 rebounding edge, and their much deeper bench outscored the two scholarship players on Vanderbilt's bench 19-3.
The Wildcats took advantage of Vanderbilt's woes by painting the inside of Memorial Gym blue with fans making themselves right at home chanting "Go Big Blue" early and often.
Kentucky took the lead for good at 8-6 on a jumper by Aaron Harrison, the first of nine straight points as the Wildcats took advantage of a nearly 6-minute scoring drought by Vanderbilt to go up 15-6.
The Wildcats led 30-22 at halftime but didn't take control until Andrew Harrison hit back-to-back 3-pointers, the second midway through the second half pushing the Wildcats' lead back to double digits. Alex Poythress added his first bucket on a layup giving Kentucky its biggest lead at 53-39 with 9:26 left.
A technical called on Poythress for delay after a dunk with 5:37 left helped Vanderbilt score five quick points including a 3-pointer by Parker to pull within 60-52 with 5:20 left.
Vandy got within 65-58 on a 3-pointer by Fuller with 2:00 left. The Commodores could get no closer as Kentucky dribbled to run out the clock and hit a couple free throws in the final minute, though the Wildcats botched an alley-oop dunk in the final seconds that drew boos mixed both for the attempt and the poor execution.