Prescott went 17-of-28 through the air for 283 yards and added 78 rushing yards on 14 carries as the Bulldogs (7-6) completed a three-game winning streak to finish the season.
Jameon Lewis led Mississippi State's receiving corps with nine catches for 220 yards.
The Owls (11-4) fell as Taylor McHargue was limited to 84 passing yards on 8-for-15 efficiency.
Charles Ross picked up 28 yards on 10 carries.
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