Kansas City catcher Salvador Perez threw out Alex Rios at the plate and picked off Alexei Ramirez at third base, and the AL Central-leading Sox kept missing chances Thursday night in a 4-3 loss to the Royals.
Eric Hosmer singled home the winning run with two outs in the ninth inning. The White Sox stayed two games ahead of Detroit, which lost in the afternoon to Oakland, with 13 games remaining.
Chicago wasted an early 3-0 lead and lost the sub-.500 Royals for the ninth time in their last 11 meetings.
"They're a tough team," Youkilis said. "They pitch well and they get timely hitting. They've got our number recently and not at a good time. Hopefully they will get really hot in their series against Detroit and play them tough."
The Royals won 12 of 18 against the White Sox this season, including one stretch of six consecutive wins.
"We've played them tough all year," Hosmer said. "It's baseball. Certain teams match up well against other teams."
The Royals now have seven games remaining with the Tigers.
"I love where we're at," Youkilis said. "Two games up is better than two games down."
But it could have been three, but the White Sox squandered early chances to pad their lead.
"Definitely runs were left out there," Youkilis said. "If we keep emphasizing it, we keep talking
Billy Butler led off the Royals ninth with a single against Jesse Crain (2-3). With two outs, pinch runner Jarrod Dyson stole second and Jeff Francoeur was walked intentionally. Matt Thornton relieved and Hosmer singled down the third base line on a 0-2 pitch.
"In that situation, it's a bad pitch, enough for him to put a bat on it," Thornton said. "I lost the game."
Greg Holland (7-4) worked a scoreless ninth for the victory.
Rios tried to score with one out in the third when Jeremy Guthrie's pitch rolled a few feet behind Perez. But Perez's toss to Guthrie covering the plate beat Rios.
"If you hesitate and don't get a good read, bad stuff happens when you do that," Rios said. "You have to be aware of the situation, with one out I could have scored on a fly ball. It was a tough read, a bad angle. I hesitated. I've got to go without hesitating."
Perez nabbed Ramirez in the fourth for his fifth pickoff, most among major league catchers.
"I don't know if they've got quicksand around third but we've been losing guys over there," White Sox manager Robin Ventura said.
After going 1 for 12 with runners in scoring position in Wednesday's 3-0 loss to Kansas City, the White Sox went 1 for 8 in those situations and stranded seven runners. Chicago is hitting .190 with runners in scoring position over the past 19 games.
"If you keep having opportunities and not taking advantage, a team like this will beat you," Ventura said.
Alejandro De Aza, Adam Dunn and A.J. Pierzynski singled in the first to take a 1-0 lead.
Guthrie committed a throwing error in the second that led to two unearned runs. He walked Dan Johnson and gave up an infield single to Alexei Ramirez, then didn't cleanly come up with Gordon Beckham's sacrifice bunt and made a wild throw to first that allowed a run to score. Dewayne Wise added an RBI grounder.
Francisco Liriano held the Royals to one hit the first four innings, but gave up a two-run triple to Johnny Giavotella in the fifth.
"Gio's hit turned it around," Royals manager Ned Yost said. "We were doing absolutely nothing until then."
The Royals tied it in the third when Butler's double scored Alex Gordon. Butler has 99 RBIs, the most by a Royals player since Carlos Beltran's 100 in 2003.
Guthrie left after six innings, allowing three runs, one earned, on eight hits. Guthrie is 4-0 with five no-decisions and a 1.75 ERA in his past nine starts, all of which the Royals have won.
NOTES: RHP Luis Mendoza, who had strep throat and was scratched from a Wednesday start, will start Friday for the Royals against Cleveland. ... Perez has picked off a franchise-record eight in 104 career games. Darrell Porter held the club record with seven in 492 Royals games from 1977-80.