Pearl replaced the fired Tony Barbee in March.
Vanderbilt (11-3, 1-0 SEC) extended its winning streak to four games in the conference opener for both teams.
The loss ended Auburn's five-game winning streak.
Auburn (8-6, 0-1) lost its 15 straight SEC road opener and 10th consecutive game to Vanderbilt.
Vanderbilt's Riley LaChance, wearing a faceguard to protect his broken nose, scored 13 points. He was named SEC Freshman of the Week for the second time Monday.
Vanderbilt's Damian Jones added 11 points and Shelton Mitchell had 10.
Auburn's Antoine Mason, a Niagara transfer who scored the Tigers first six points, led the visitors with 16.
Vanderbilt outrebounded Auburn 47-27, including a 35-17 edge on the defensive glass. Commodores forward Luke Kornet and Siakam each grabbed 10 rebounds.
Auburn's K.T Harrell, who entered the game as the SEC's second-leading scorer (17.9 ppg) was held to eight points on 3 of 9 shooting.
Auburn's Jordon Granger hit a 3-pointer to cut Vanderbilt's lead to 55-50 with 2:13 left.
LaChance answered with a layup that increase the Commodores' lead to 57-50 with 1:05 left.
Vanderbilt held a two-point lead when it went on a 12-0 run, boosting the Commodores' advantage to 25-11 on Mitchell's layup with 7:10 left in the first half.
Midway through the run Pearl called a timeout to try to change the momentum, but the Commodores kept pouring it on.
Auburn came out cold, missing 16 of its first 20 shots.
Vanderbilt hit 46.4 percent of its shots from the floor during the first 20 minutes to take a 33-19 halftime lead.
The Commodores nearly doubled Auburn's rebound total in the first half with a 24-13 advantage.
Auburn narrowed the gap to 43-38 on Mason's layup with 10:42 left.
Vanderbilt rallied, stretching its lead to 50-38 on LaChance's 3-pointer with 9:10 left.
Auburn was seeking its longest winning streak since a seven-game win streak in 2008-09.
Pearl was 3-3 at Memorial Gym at Tennessee, including a 72-69 loss when Tennessee was ranked No. 1 in 2008.
His SEC winning percentage of 67.1 trails only Kentucky's John Calipari (76.2).
Auburn hasn't won at Memorial Gym since 2000.
Auburn's Cinmeon Bowers, a junior college transfer who entered the game as the SEC's leading rebounder, grabbed nine boards.