Hot-shooting Texas Southern led by two points at the break, but a fast start to the second half helped Clemson gain control and ultimately pull away for a 76-56 win.
Jaron Blossomgame led the way for Clemson with 22 points and 9 rebounds, while Sidy Djitte came off the bench to log his first career double-double with 13 points and 11 rebounds.
Texas Southern shot 7 of 17 from three in the first half and held a 33-31 lead at halftime, but a 21-4 run by Clemson to open the second half was too much to overcome as Texas Southern made just 2 of 12 from distance the rest of the way.
Clemson outscored Texas Southern 45-23 in the second half while making a concerted effort to get the ball inside for easy baskets for Blossomgame and Djitte. Clemson shot 50% from the field in the game, with many of those points coming in the paint.
Jordan Roper scored 14 points for Clemson, while Donte Grantham and Landry Nnoko added 11 apiece.
Malcolm Riley scored 23 points to lead Texas Southern.
Clemson's will take on UMass in the first round of the MGM Grand Main Event in Las Vegas on Monday at 9:30 p.m.