Carlos Gomez drove in a career-high five runs and Minnesota had an unusually productive afternoon against Buehrle in a 13-7 victory over Chicago.
Buehrle (9-3) gave up eight runs and 10 hits in 3 1/3 innings, his shortest outing of the season.
"He left a few balls up and over the middle of the plate," said Brendan Harris, who went deep and doubled twice in three at-bats against Buehrle. "That's more than I've seen in the six or seven times I've faced him."
Gomez and Denard Span also homered against Buehrle, who has beaten Minnesota more times than any other opponent. Coming into the game, Buehrle was 23-13 with a 3.72 ERA lifetime against the Twins and 2-0 with a 1.35 ERA this season.
"I think I threw five pitches where I wanted and I think three of them got hit," Buehrle said. "It was one of those days where everything was cutting when I wanted it to sink. Even when I was throwing warmup pitches, I threw a changeup and it was cutting on me. It was one of those days where I didn't have my good stuff."
Harris and Span each had three RBI. Gomez finished with three hits and scored three times.
"He left some balls up today and we put some good swings on it," Twins manager Ron Gardenhire said of Buehrle. "You don't see that too often against that guy."
Scott Baker (7-7) gave up five runs and six hits in 6 1/3 innings for the Twins, who took two of three from the White Sox heading into the All-Star break.
The signs were there from the beginning that this was not going to be Buehrle's day.
The big lefty made what looked to be a very heady play in the first when Span's bunt rolled down the first-base line. Buehrle slid as he gave chase, but deftly maneuvered around the ball without touching it as it trickled foul.
The athletic play took away what would have been a sure hit for Span, but two pitches later he homered to right field.
Gomez hit a three-run homer in the second and Harris added an RBI double to give the Twins a 5-0 lead and start activity in the White Sox bullpen. When Harris hit a two-run homer to make it 8-1, Buehrle was done.
"This year, I don't remember seeing Buehrle have trouble like he did today," manager Ozzie Guillen said. "He had trouble against the wrong team in the wrong ballpark. That's what you're going to get."
Jim Thome hit his 555th career homer, a three-run drive in the sixth, and Alexei Ramirez beat out an infield hit with the bases loaded in the seventh to make it 8-5. But Matt Guerrier got Jermaine Dye to pop out to second to end the threat.
Span added two walks and two stolen bases, and Gomez, the precocious 23-year-old known as "Go-Go" in the clubhouse, humorously tried to stretch a ground-rule double into a triple before third base coach Scott Ullger pointed him back to second.
His two-run single in the seventh gave the Twins some breathing room at 10-5 after the White Sox creeped back into the game.
"It was a great day," said Gomez, who was amped about heading home to the Dominican Republic to see his wife and newborn child.
The Twins did all their damage offensively without any help from AL batting leader Joe Mauer, who went 0 for 5 and struck out four times for the first time in his career.
"I think everybody should keep their ticket because they saw something that nobody will see again and that's Mauer strike out four times," Guillen said. "I'd keep the ticket and I'm going to keep the lineup card because that isn't going to happen too often."
- White Sox rookie 3B Gordon Beckham had two errors, including one in the seventh that allowed a run to score.
- Span's drive in the first was his first career leadoff homer.
- Twins C Mike Redmond snapped an 0-for-16 slump with a single in the second inning.
- Dye had some fun before the game, throwing a couple of balls in from the outfield during a mascot T-ball game. Justin Morneau must have missed it because he was thrown out by RF Dye while trying to turn a single into a double in the fourth.