Karl Nicholas led five Tigers players in double figures with 16 points and 12 rebounds while Jordan Gilliam and Justin Hopkins each added 15 as Texas Southern beat the top two seeds in the tournament to reach the field of 68.
Faite Williams led Prairie View A&M (16-5) with 14 points, Jawaun Daniels chipped in with 13 points and D'Rell Roberts added 10 as the Panthers suffered their first conference loss of the season.
Texas Southern handles Prairie View to punch ticket to March Madness
A back-and-forth battle early, the Prairie View built a 14-8 lead after a Williams jumper. Texas Southern tied the game with a 6-0 run, but Daniels responded with five quick points, only for the Tigers to battle back again.
After a Cam Mack jumper tied the game again at 24-24, Texas Southern went on a 12-4 run to close the first half to take a 36-28 lead into the halftime break. The Tigers then opened the second half on a 9-0 run to go up by 17.
A dunk by Nicholas eventually increased the lead to 21 and Texas Southern, who shot 51 percent from the field, never looked back as the Tigers clinched their first NCAA bid since 2018.
"Gratifying the way we had to do it", said Texas Southern head coach Johnny Jones. "Through the pandemic, weather problems including the last two games of the regular season games we had to play. These guys stayed together, stayed focused, they never wavered.
"I'm very proud of the way our team battled through adversity to get to this point. This championship means a lot to our players and to Texas Southern University. We're excited where this program is headed and we look forward to participating in the NCAA Tournament."
Tournament MVP Michael Weathers added "it feels amazing, we had one job, one mission and we got it done. Amazing."