Jeremy Smith had team highs of 17 points and eight rebounds for the eighth-seeded Colonels (10-20). Dantrell Thomas added 15 points.
Nicholls State shot a tournament-record-low 23 percent, made only 4 of 35 3-pointers and was outrebounded 43-30.
The 48-point margin was the largest in tournament history.
The Mavericks held Nicholls State scoreless for 8:28 and rushed to an early 22-4 lead. A 12-0 spurt put them ahead 50-19 early in the second half.