Wallace passed for 151 yards with two interceptions on 22-of-32 efficiency as the Rebels (7-6) won for the ninth time in their last 10 bowl game appearances.
Mathers ran for a 62-yard score and Barry Brunetti added a rushing touchdown for Ole Miss.
Pittsburgh (6-7) dropped its second straight Compass Bowl after winning the event in 2011.
Tino Sunseri led the Panthers with a pair of TD passes, going 16-for-32 through the air for 185 yards with an interception.
Devin Street grabbed a scoring pass, finishing with 83 yards on seven receptions.
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