Sikeston, which is now 4-0 in the conference, scored seven runs in the final three innings to break open a 1-1 game.
A Scotty Keenan home run over the right field fence in the top of the fifth broke the tie and seemed to spark the Bulldogs.
Poplar Bluff coach Tim Harmon sensed something bad could happen when Keenan stepped to the plate with two outs and a base open.
"I had just got through telling one of my assistants, 'this guy scares me to death,'" said Harmon. "Because to me he's one of the most dangerous hitters they've got in the lineup. I know they got the two big sticks in the middle. I almost walked him to get to the next guy. We threw him a fastball outside but it tailed back over the middle of the plate and he just deposited it over the fence there. It takes a good poke to get one out of here."
The Bulldogs responded with two more runs in the top of the sixth when Richard Landers' seeing-eye single up the middle plated Blake DeWitt and Jacob Priday to take a 5-1 lead.
The Mules (4-3, 4-1 in SEMO Conference) cut the lead to 5-3 in the bottom half of the inning but the Bulldogs put the game out of reach in the seventh with three more runs.
A DeWitt run-scoring double to centerfield brought home Lance Rhodes. The Bulldogs added two more runs when DeWitt scored on a wild pitch and Priday came home on an error.
"We're still a kind of sluggish out of the gate," said Sikeston head coach Kevin Self. "I don't know what it takes. Maybe we've got to see a guy once or twice. But sometimes you wait that late and you don't scratch any."
Poplar Bluff sophomore hurler John Patty threw 5 2/3 innings in taking the loss. He shut down the Bulldog offense through the first four innings, but started to lose control in the fifth after the Keenan home run.
Self knew Patty would be tough after pitching a tough game in last year's SEMO Conference Tournament before losing to the Bulldogs 2-1.
"He gave us fits last year," said Self. "We hit him a little better today than we did the last time we played them in the SEMO Conference at Capaha last year. Poplar Bluff's much-improved. They're playing well and they were (4-0) in the conference coming in. I knew we'd have to play well to beat them. We gave them more than three outs in an inning a couple times and that just about came back to bite us big."
Sikeston took a 1-0 lead in the top of the second on a Cullen DeHart run-scoring single.
The Mules tied it in the bottom of the second on Steve Atteberry's RBI-double to left field.
The Mules had a chance to take the lead in the bottom of the fourth when Atteberry singled to left field.
But Priday, playing in left for the first time, charged hard and gunned out Seth Blackwell at the plate.
"We challenged them but Priday made a great throw," said Harmon. "The runner probably rounded too far, but you've got to take your shots when you get them against Sikeston. You can't sit up there and rely on three hits back-to-back-to-back against any of their pitchers. We were going to take shots every chance we could get."
Bulldog hurler Bryce Wibbenmeyer got the win, throwing five innings and allowing one run off six hits. He walked two and struck out two.
DeWitt threw two innings of relief and allowed two runs off four hits. He got out of a jam in the bottom of the sixth by striking out Justin Newton with the bases loaded to end the threat.
"When the game's on the line, DeWitt, he's the guy you want out there because he's going to gut it up no matter if he has his good stuff on any given day," said Harmon.
DeWitt, Priday and Landers each had two hits for the Bulldogs. Priday scored three runs.
Atteberry led the Mules with three hits. Cannon Bagby had two doubles and two runs.
Sikeston and Poplar Bluff will both play in the McCracken County Wood Bat Tournament on Friday and Saturday.
Sikeston will play Millington, Tenn., at 11 a.m. at Reidland High School on Friday. They follow up that game with a 1 p.m. matchup with Reidland.