BYU hit the floor hot from the outset and there was little Southern Miss could do as the Cougars rolled to a 79-62 game at Reed Green Coliseum.
BYU will take on Baylor on Tuesday in the NIT semifinals.
USM jumped out to an early 5-0 lead, but it was pretty much all BYU from that point forward.
Brock Zylstra hit 4-of-5 3-pointers early in the game, and that seemed to set the tone for the Cougars.
Tyler Haws led all scorers with 25 points while Zylstra had 23.
First-year USM coach Donnie Tyndall was once again thankful for the fan support tonight with 7,679 showing for Wednesday's game.
Tyndall also gave credit to the three USM seniors who ended their career Wednesday night - Jonathan Mills, Dwayne Davis and Rashard McGill.
"I told those three guys how proud I am of them," Mills said. "Mills, I told him he was the toughest kid I've ever coached in my life. I've had some tough, hard-playing guys and he's the toughest kid I've ever coach. Dwayne Davis, five years ago, we moved him out of our program at Morehead State. Now, he's on track to graduate in May. He was first-team all-league and he had an unbelievable one year in Division I basketball. Rashard, I talked with my staff in the first week of practice and I said I didn't think he'd ever play for us. He improved so much by the end of his senior season by how hard he worked and he practiced the right way. He might have been the best sixth man in the league by the end of the year. I challenged the younger guys to meet the leadership and effort they gave."
Daveon Boardingham led USM with 18 points while Jerrold Brooks added 13
USM ends the season with a record of 27-10, setting the school's Division I record for most wins.
BYU ended USM's 30-game home winning streak over non-conference opponents.