Reggie Agbeko had 12 points and nine rebounds off the bench for Saint Louis (5-12, 1-4 Atlantic 10), which led by as many as 16 points in the first half.
George Mason (12-6, 2-3) trailed 31-18 at halftime but made 5 of its first six 6 field goal attempts out of the break after a 5-for-22 performance in the first half to get within 33-29.
Ian Boyd's layup tied it at 42, a 3 from Jaire Grayer tied it at 45, and Jalen Jenkins' offensive rebound and putback with 3:54 remaining gave the Patriots a 54-52 lead, their first lead since the opening two minutes of the game.
But Saint Louis' defense forced George Mason into misses on the Patriots' next five field goal attempts, and Mike Crawford and Davell Roby each made a pair of free throws in the final 21 seconds to ice it.
Grayer made four 3s and scored 16 points for George Mason.
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