The victory guarantees the Wildcats (6-4, 4-3) at least a .500 record in both the regular season and Southeastern Conference, virtually assuring them a spot in postseason play.
Representatives of five bowl games were on hand to scout both teams, but the loss knocks Vanderbilt (4-7, 1-6) out of contention. The Commodores, who haven't appeared in a bowl since 1982, lost for the fifth time to their last six meetings with the Wildcats.
Kentucky tailback Rafael Little, playing for the first time in more than a month after undergoing arthroscopic knee surgery, gave the Wildcats the lead for good midway through the fourth quarter with a 2-yard touchdown run. Little finished with 20 carries for 132 yards. He also caught eight passes for 114 yards.
Faced with fourth-and-goal on the Kentucky 2 midway through the fourth quarter, Vanderbilt had a chance to regain the lead. But Kentucky cornerback E.J. Adams picked off Chris Nickson's pass and ran it back to midfield.
Woodson then found DeMoreo Ford open in the end zone for a 27-yard touchdown to give the Wildcats a 31-20 lead, and Kentucky cornerback Marcus McClinton stopped Vanderbilt's next drive with another interception near the end zone.
Woodson iced the victory by throwing his fourth touchdown - a 57-yarder - to Burton. The Kentucky quarterback has 24 touchdowns this year - four times as many as he had last year.
It had been several years since these two teams met in such an important game. The win gave Kentucky a 38-37-4 lead in the all-time series.
Although it ended up being a battle of defensive futility, neither team got on the board until midway through the second quarter, when Kentucky's Lones Seiber nailed a 28-yard field goal.
Kentucky had started the drive on its own 4, after Wesley Woodyard ended a Vanderbilt threat by stripping the ball from Nickson just before the goal line.
Nickson led the Commodores with 71 rushing yards and two touchdowns. He also threw for 446 yards and one score - a 41-yard pass to Bennett with no time left and the game out of reach.
But every time Vanderbilt started to threaten, the Kentucky tandem of Woodson and Burton went to work.
First, Burton caught a flat pass from Woodson and galloped nearly untouched for 60 yards. Then, Woodson, under fierce pressure from a Vanderbilt blitz, pointed to the spot of the end zone where he wanted Burton to go. His receiver followed the direction and caught Woodson's five-yard pass for the touchdown.
Burton had 11 catches for 171 yards. He also nearly added a kickoff return touchdown to his accomplishments, but it was called back on a holding penalty.
Both teams would miss field goals before the half, preserving a 10-7 lead for Kentucky.
Although Little saved most of his heroics for the second half, he proved on Kentucky's first possession that his knee was fine. He ran for three first downs, including a 49-yard burst that set up a 27-yard field goal attempt by Seiber, but the kick hit the left upright and was no good.
The usually steady Wildcats special team units were shaky in the first half. Besides Seiber's two missed field goals, Tim Masthay had a punt blocked - Vanderbilt's first in two years. Masthay injured his shin on the play and didn't return.