The victory was the fifth straight for the Commodores, who improved to 20-6 overall and 8-4 in the SEC.
Auburn, which has lost its last two games, fell to 9-17 for the season and 2-10 in the league.
Earnest Ross led the Tigers with 19 points and 10 rebounds. He finished with five assists, six turnovers and two steals.
Auburn was playing even with the Commodores for much of the game. The score was 42-42 with 14:21 left after Ross hit a three-pointer. However, Vandy scored 14 uncontested points and took control.
"We kind of broke down defensively," Ross said. "We stopped playing. We let go of the rope."
Once Vandy got a solid lead the Commodores never let their foot off the gas as the SEC's leading scorer, John Jenkins, came up with 16 of his game-high 22 points in the second half. He did most of his damage from long range hitting 5-11 threes as the Commodores made nine treys on 21 attempts while Auburn hit 5-12.
"They made shots in the second half so we can give them credit there," said Auburn coach Tony Barbee, who was not pleased with his team's 19 turnovers. "I thought our offense just made some horrible decisions. We made the worst decisions with the basketball that I have ever seen in the second half.
"We had guys wide open on backdoors and wide open on post-ups," Barbee said. "Our guys just had the ball taken right out of their hands. It is disappointing."
"In the second half we started to hang our heads," Barbee said. "We let our lack offense, our lack of toughness in securing the ball and making good decisions affect our defense...We stopped doing what we did in the first half."
Vandy got 20 points and 10 rebounds from Swedish forward Jeffery Taylor, who hit 7-13 shots. Point guard Brad Tinsley scored 16 points for the Commodores and played 33 minutes without a turnover.
"They are a veteran team and they played that way," Barbee said. "They don't panic."
Both teams played with intensity throughout the first half. Auburn came out in a full-court press and a man-to-man and that kept Vandy off its game offensively.
The Tigers, who later switched to half-court pressure and a two-three zone, hung with the 18th-ranked Commodores throughout the half as the teams swapped the lead.
Vanderbilt led 28-26 at halftime, but Jenkins picked up his third foul with 1:39 left before intermission and headed to the bench as Ross hit two free throws to tie the game at 24-24.
Earnest Ross shoots for the Tigers.
At the break the Tigers were hitting 45 percent of their field goals on 9-20 shooting. Auburn was 1-3 on treys and 7-12 at the foul line.
The Commodores were 9-25 from the field for 36 percent. Vandy hit 4-14 threes and 6-9 first half free throws. Each team pulled in 16 rebounds. Vandy turned the ball over 10 times to seven for the Tigers in the first 20 minutes.
The rebounding stats changed in the second half as Vandy finished the game with 35 to 28 for Auburn. The Commodores finished the contest shooting 48 percent from the field, 42.9 from three and 71.4 percent at the foul line making 20-28.
Auburn shot 44 percent from the field, 41.7 percent on threes and made 64.7 percent at the foul line hitting 11-17.
Vandy coach Kevin Stalling said, "I don't think we had the same energy level in the first half that we've had in some recent games. Some of that is natural. I think you have a bunch of just really tough ones in a row and at some point you're going to have a little bit of a letdown, probably.
"We had one in the first half," he said. "We bounced back in the second half. It was not a case of taking them lightly. We knew they were going to be tough. We knew they would be good.
"I was really impressed with their crowd," Stallings said. "They're having a tough season and they really had a nice crowd today, I thought. They have a beautiful new facility here."
The Tigers return to action on Wednesday at 7 p.m. as they travel to Tuscaloosa to take on Alabama. "It's a great rivalry," said Kenny Gabriel, who scored 13 points vs. Vanderbilt. "We just have to go over there and play hard. If we play hard we will have a chance."