The Mules, who received 177 yards rushing from senior Zach Ferguson, improved to 5-2.
Jackson fell behind on Poplar Bluff's first play from scrimmage as Eljie Johnson rumbled 77 yards for a touchdown just 19 seconds into the game.
Jackson fumbled on the ensuing kickoff to set up the Mules' second touchdown.
Ryan Marble provided Jackson's lone points in the second quarter when he blocked a punt and recovered it in the end zone.
Poplar Bluff led 13-6 at halftime and added single touchdowns in the third and fourth quarters.
Check back later or read Sunday's Southeast Missourian or Daily American Republic for more on this game.