Jacoby Ellsbury's towering drive kept going as Moses Sierra retreated in right field. Sierra made a leaping try as he reached the wall, but it was way over his outstretched glove.
This time, the New York Yankees had the biggest swing on the South Side of Chicago.
Ellsbury homered with two outs in the 10th inning, and the Yankees snapped an eight-game road losing streak against the White Sox with a 4-3 victory on Saturday.
"I knew I hit it well," Ellsbury said. "I thought I might have hit it a little too high, but great feeling once it went out. Excited to get that win."
The Yankees scored three times in the ninth against Ronald Belisario and then grabbed their first lead of the day when Ellsbury connected against Zach Putnam (2-1) for his second homer.
Dellin Betances (3-0) pitched a perfect inning for the win and David Robertson finished for his 10th save in 11 chances, bouncing back nicely after yielding Adam Dunn's game-ending homer in Chicago's 6-5 victory on Friday night.
Adam Eaton singled and stole second with two down, but Robertson struck out Gordon Beckham to end the game.
"Last night was a tough one. The team battled really hard, we got the lead and I wasn't able to nail it down," Robertson said. "They did the same thing today and I was not going to let them down today."
John Danks pitched eight shutout innings for the White Sox, who had won four of five. Beckham and Eaton had three hits apiece.
"Just trying to get the ball, go, throw strikes and let these guys work behind me," Danks said. "It worked out. They made some good plays on some balls that were well placed and caught some breaks. You need that in this game, especially against that team."
Danks handed a 3-0 lead over to Belisario after his best start of the season. The right-hander yielded a one-out single to Ellsbury, but was in position for his third save when he struck out Mark Teixeira for the second out.
Then it all fell apart in a hurry for the closer, who has allowed at least one run in each of his last three outings.
Ellsbury took second on fielder's indifference and scored on Alfonso Soriano's ground-rule double. Yangervis Solarte singled home Soriano and moved to second when Belisario walked Ichiro Suzuki.
Pinch-hitter Brian McCann then completed the comeback with a bloop single into center field, driving in Solarte with the tying run. Brendan Ryan grounded out to end the inning, and the crowd of 33,413 booed as Belisario made his way to the dugout.
"Obviously huge at-bats to get us going," Yankees manager Joe Girardi said. "We hadn't done much up to that point."
Danks allowed three hits, struck out four and walked none. The left-hander was 1-4 with an 8.23 ERA in his previous five starts.
Teixeira's ground-rule double in the fourth was New York's only hit before John Ryan Murphy and Ryan had consecutive two-out singles in the eighth. But Danks got Brett Gardner to fly out to right to end the inning.
Vidal Nuno pitched seven-plus innings for New York in the longest start of the season for the converted reliever. He allowed nine hits, struck out five and walked one.
The White Sox did all their damage against Nuno in the first. Eaton and Beckham started the inning with consecutive singles, and Dayan Viciedo then made it 1-0 with a double into the gap in left-center. Dunn drove in Beckham with a sacrifice fly and Viciedo came home on Alexei Ramirez's groundout.
"I was up in the zone the first inning, first half of the lineup and it was just making pitches," Nuno said. "It was a long game, guys came back and it was unbelievable how we came back and kept fighting."