The Yankees moved into a tie with Boston for the AL East lead. The teams begin a three-game series at Fenway Park on Friday night.
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Russell Martin hit a three-run homer in the ninth to break open the game and send Chicago to its sixth consecutive loss. He drove in four runs.
Nova (10-4) pitched 7 2/3 innings and won his sixth consecutive decision. He held Chicago to one run and six hits and didn't walk a batter.
Robinson Cano homered, singled, walked and scored a pair of runs as the Yankees won their sixth straight against Chicago, a streak during which they've outscored the White Sox 49-14.
The White Sox have lost six straight after getting to the .500 mark and drawing within three games of the lead in the AL Central last Friday.
Chicago absorbed its first four-game sweep at home since dropping four in a row to Boston from Aug 23-26, 2007. The last time the White Sox were swept at home in a four-game set against New York was June 17-20, 1976.
Paul Konerko had two singles for a quiet White Sox offense in his first start since Sunday. He missed the three previous games with bruised left leg. Adam Dunn hit a home run in the ninth.
Phil Humber (8-8) lost his fourth consecutive start. He went 6 1/3 innings, allowing five hits and four runs.
Entering the game, the players currently on the Yankees' roster came into the game a combined 0 for 18 lifetime against Humber. He retired the first four batters on Thursday before Cano came up in the second.
With one out in the inning, Cano lined the first pitch he saw from Humber into the left-field bullpen for the first run of the game. It was Cano's 18th home run of the season and second in as many games after he had gone 14 games without a longball.
Nova had good stuff early, retiring the first seven White Sox in order, the last three on strikeouts.
The streak was broken when Alejandro De Aza beat out an infield grounder to shortstop Derek Jeter. That gave De Aza, who was 4 for 4 on Wednesday in an 18-7 loss to New York, five consecutive hits.
De Aza then stole second, went to third on Brent Morel's single to right and scored on Juan Pierre's sacrifice fly for a tie at 1.
The Yankees regained the lead in the sixth thanks to the speed of Brett Gardner, who started the inning with a double to right and went to third on Jeter's sacrifice bunt.
Curtis Granderson hit a hard grounder to Dunn at first base and Gardner broke for the plate. Dunn stepped on the bag to retire Granderson and threw home, but Gardner slid home safely just ahead of the tag by catcher A.J. Pierzynski.
Humber seemed to tire in the Yankees' two-run seventh. Cano led off with a single, Nick Swisher walked and Jorge Posada hit an RBI single for a 3-1 lead.
That was it for Humber, who was replaced by Jesse Crain after throwing 94 pitches. Swisher scored on Martin's sacrifice fly to deep center,
Konerko had been out since being hit in the left knee by a pitch against Boston last Sunday. Manager Ozzie Guillen said Konerko would be limited to designated hitter duty for a few days. ... Bartolo Colon will start for the Yankees in the series opener against Jon Lester. New York is 454-458 all-time at Fenway. However, the Yankees are 1-8 vs. Boston this season and have lost seven straight at Fenway. Colon has lost both of his starts against the Red Sox this season, once each at Boston and New York. ... Mark Buehrle gets the call for the White Sox in their opener at Minnesota in a key series for two teams scrambling to stay in the AL Central race. The Twins have beaten the White Sox in seven of eight meetings this season and have won 29 of their past 36 against Chicago. Buehrle has posted a 2.03 ERA over his past eight starts but is only 2-1 over that stretch. He has allowed three runs or fewer in 16 consecutive starts. ... White Sox speedster Juan Pierre was thrown out stealing in the sixth. He only 16 for 29 on the basepaths this season.