Malik Smith went 3 of 4 from behind the arc and finished with 17 points for Florida international (14-12, 9-8).
On top 42-38 at halftime, Florida International started the second half on a 9-3 run, capped by Deric Hill's 3-pointer with 17:03 remaining to go ahead 51-41.
Western Kentucky (13-14, 7-9) trailed by as many as 15 points after intermission.
T.J. Price's 3-pointer with 23 seconds left cut the Hilltoppers' deficit to four, 84-80, but the Panthers made 3 of 4 free throws to seal the victory.
Florida International shot 52.2 percent (12 of 23) in the second half while Western Kentucky shot 43.3 percent (13 of 30).
Price led the Hilltoppers with game-highs of 22 points and six assists, but also had five turnovers.
Former Kentucky guard Ed Davender, the only Wildcat with at least 1,500 points and 400 assists, has died. He was 49.
Guard Naz Mitrou-Long, whose 2015-16 season ended in December due to hip problems, has been granted a hardship waiver for the coming season, Iowa State said.
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