Youkilis delivered the biggest blow against Nova with his fifth-inning blast, the slugger's 15th homer of the year and third career grand slam, clearing the right-field wall as Nick Swisher tracked it to the Yankees' bullpen but ran out of room.
"I was trying to drive the ball to the outfield, get a runner in," Youkilis said. "That's what I was trying to do, and I was very fortunate it got over the fence."
As four White Sox baserunners circled the bases, Nova stood with his hands at his hips on the mound and stared toward home plate, a much different scene than Yankees fans saw last year when the hurler went 16-4 with a 3.70 ERA.
"He's struggled, no doubt," Yankees manager Joe Girardi said. "The second half, he has struggled. He has not located like he did in the first half. His offspeed [stuff] has not been consistent. We've just got to keep working at it. That's all you can do."
Since returning from the All-Star break, Nova has gone 1-4 with a 7.28 ERA in eight starts, spoiling a first half that saw him cruise into the rest with 10 victories and a 3.92 ERA.
"He's always been kind of a loose arm that slings it up there," catcher Russell Martin said. "Right now, all I see is that the ball is being left up a little bit, especially his fastball. I'd like to see his fastball a little more down -- more consistently down in the zone."
Nova also served up a fourth-inning Paul Konerko home run, his 21st, among the seven hits he permitted. Chicago's first run off Nova came in the second inning as Alex Rios tripled and scored on A.J. Pierzynski's sacrifice fly.
"I was good early," Nova said. "Then, with the bases loaded [in the fifth] ... it seems like when I have men on base, that's something I've got to look at."
Nova walked two and struck out three, throwing one wild pitch. He said that he is not concerned about losing his spot in the rotation, though with both CC Sabathia and Andy Pettitte on the comeback trail, nothing seems completely locked in.
"We haven't talked about what we're going to do," Girardi said. "We're not that far along."
The Yankees, who maintained a four-game lead in the American League East with the Rays' 1-0 loss to the Royals in 10 innings, managed two runs in six innings against Chicago starter Francisco Liriano.
"We had some opportunities," Girardi said. "He just made some big pitches when he had to. We made him work; we just weren't able to get a lot of runs off of him."
Derek Jeter didn't wait long to surpass Eddie Murray for sole possession of 11th place on baseball's all-time hits list, slugging his 252nd career home run to lead off the game.
The hit marked the 3,256th of Jeter's career, nudging him past Murray, and it knotted him on the all-time home run list with several familiar names, including former Yankees manager Joe Torre.
Curtis Granderson logged an RBI later in the first inning on a fielder's choice, scoring Swisher, but the Yankees were handcuffed from there by Liriano. The lefty struck out seven and permitted six hits, walking three batters.
"It was touch-and-go in the beginning, but this team will make you use a lot of pitches," Chicago manager Robin Ventura said. "He did battle through it and got sharper as the game went along. He just made pitches and at least got us to a point where we could go to the bullpen, and guys came in and did a good job."
Martin slugged a solo home run, his 14th, in the seventh off Jesse Crain to trim New York's deficit, but Derek Lowe surrendered Chicago's final run in the bottom of the eighth after giving up a leadoff triple to Pierzynski.
Nova spoke in a soft hush as he stood in front of his locker and nodded toward the laptop computers in the corner of the visitors' clubhouse, saying he'd spend time reviewing video of his starts in hopes of finding the flaw keeping him from success.
It seemed a long way from the boastful statement Nova delivered in April, when he was flush with victories and proclaimed that he might be the best pitcher in the world at that moment. About now, he'd settle for just stringing a couple of wins together.
"I don't know if he's losing confidence; I think he trusts his ability," Martin said. "He might be getting a little frustrated out there, not getting the results that he wants. The effort's there. He pitches with passion. He's a competitor.
"He's just not getting the results that he wants. He's just got to keep fighting through it. There's going to be times that are tough, and right now, he's going through a rough patch."