Cannen Cunningham scored 17 points to lead
Ben Moore added 11 points in the Mustangs' first NIT since 2000. Nick Russell chipped in 10.
SMU (24-9) used a 23-7 run in the second half to erase a 35-29 deficit, scoring inside and hitting free throws to balloon the lead to 52-42 with 8:16 left.
However, less than two minutes later, the refereeing crew determined the Mustangs inadvertently were given a one-and-one opportunity too early, and they removed a point from the hosts to make it 51-44 with 7:24 left.
Luke Nelson led Irvine (23-12) with 13 points and Alex Young chipped in 10.
SMU will face either LSU or San Francisco in the second round
Pitino criticized the selection committee Wednesday for pitting his fourth-seeded and defending national champion Cardinals against 13th-seeded Manhattan, which is coached by Pitino's former assistant, Steve Masiello. Louisville and Manhattan open tournament play Thursday night in the Midwest Region.
"I think the pairings sometimes lack common sense," Pitino said. "I don't think they would put somewhere down the road Duke-North Carolina so … the matchups don't make sense to me. I'm OK with the seedings. I'm not OK with the matchups.
Police confirmed Wednesday that they are investigating an allegation that two Providence basketball players sexually assaulted another student on the Rhode Island campus in November.