Kevin Youkilis broke open a tie game with a grand slam in the fifth inning, and the Chicago White Sox led the rest of the way en route to a 7-3 win over the New York Yankees at U.S. Cellular Field.
Paul Konerko went 2-for-4 with a solo homer while Gordon Beckham also had two hits and drove in a run for the Sox, who had lost three in a row before taking the first two meetings of this three-game series.
Francisco Liriano (5-10) earned a second straight victory after allowing two runs on six hits over six frames. He struck out seven and walked three.
"We had some opportunities, but (Liriano) made some big pitches when he had to," Yankees manager Joe Girardi said. "We made him work, we just weren't able to get a lot of runs off him."
Ivan Nova (11-7) also pitched six innings, but surrendered six runs on seven hits to take the loss, New York's fourth in its last six games.
Derek Jeter homered on the game's first pitch, and the Yankees were knocking on the door for more when they loaded the bases with one out later in the first.
Liriano limited the damage to one more run on Curtis Granderson's fielder's choice groundout, and Chicago scored the next six runs to take control.
Alex Rios tripled leading off the second and trotted home on A.J. Pierzynski's sacrifice fly, and Konerko's 21st homer of the season tied it in the fourth.
Alexei Ramirez sparked the Sox's pivotal fifth with a one-out double, and a walk to Beckham and a single by DeWayne Wise loaded the bases for Youkilis. Nova threw the first ball in the dirt and the second just off the outside part of the plate.
Youkilis reached out at the second offering and appeared to hit it off the top of his bat. But the fly ball to right field kept carrying and narrowly cleared the right-field wall for his third career grand slam.
"I was trying to drive the ball to the outfield, and I was fortunate it got over the fence," Youkilis said.
Russell Martin belted a solo homer off Jesse Crain in the seventh to cut the Yankees' deficit to 6-3, but Chicago got the run back in the eight as Pierzynski legged out a triple and scored on Beckham's two-out base hit.
Brett Myers shook off a leadoff walk in the ninth to secure Chicago's first season series victory over the Yankees since 2003.
Chicago has won four of six in the season series, which ends Wednesday ... The White Sox recorded 12 hits, four from Wise but none from Dayan Viciedo, who went 0-for-4 to snap an 11-game hitting streak ... Jeter's 29th career leadoff homer moved him past Eddie Murray for sole possession of 11th on the all-time hits list with 3,256 hits ... Before the game the White Sox placed outfielder Alejandro De Aza on the 15-day disabled list and recalled outfielder Jordan Danks from Triple-A Charlotte.