The loss snapped the Rams' 16-game winning streak.
Matthews scored all of his 14 points in the second half.
The Rams had won 16 straight since the senior returned after missing six games with a broken left wrist.
Matthews was hurt late in the first half of an 85-67 win over Richmond on Tuesday.
The Rams (21-4, 13-1 A-10) still have the inside track to clinch the school's first Atlantic 10 regular-season title. With the upset, the Bonnies gave their chances of an at-large NCAA bid a nice boost.
The Bonnies haven't made the NCAA tournament since 2012, and they have attracted some national attention for their performance this season, including receiving three votes in the latest AP poll.