The win, only their fourth of the season, was the Golden Panthers' first victory over SMU in 22 years and was revenge for their 6-0 loss to the Mustangs in last year's conference tournament.
FIU went into the game with a 3-13-2 record but used a stifling defense to shut down SMU after the Mustangs took the lead on Scott Geppert's seventh goal of the season off an assist from Adrian Chevannes in the seventh minute.
FIU blitzed SMU, the defending Conference USA champion, with a second-half barrage. Sophomores Juan Guerra and Christian Caporaletti and freshman Steven Jair Cabas scored for the Golden Panthers.
"We gave up an early goal, but then everybody stepped it up," said first-year FIU coach Munga Eketebi. "Defensively we were solid. We didn't give up any penetration. And for a change, we scored goals."
FIU, the No. 7 seed, meets No. 2 seed South Carolina in Friday's semifinals.
No. 6 Marshall upset No. 3 Kentucky, 3-1, and will play the winner of Thursday's game between top-seed Tulsa and host UAB. Their quarterfinal was postponed because of inclement weather.