Roquez Johnson netted 18 points and Fred Thomas added on 16 for 14th-seed MSU (14-18), which advances to take on sixth-seed Ole Miss in the second round. Gavin Ware contributed 11 points as well.
Damian Jones tallied 16 points for 11th-seed Vanderbilt (15-16). Dai-Jon Parker and Rod Odom had 15 points apiece and Kyle Fuller tacked on 11.
MSU shot well from beginning to end. It connected on 60.9 percent from the floor in the first half, claiming a 36-31 lead at the break, and then netted 58.1 percent in the final 20 minutes.
Vanderbilt remained within striking distance in the first period, shooting 48 percent from the field, but it fell to 41.9 percent shooting during the final frame.
The Bulldogs had a 33-25 advantage on the glass and assisted on 21 of 32 made field goals.