Neither rattled nor perturbed by two popups that weren't caught, Buehrle hung around for six innings and the Chicago White Sox got a pair of key two-out hits in the fifth inning and solo homers from Paul Konerko and A.J. Pierzynski to beat the Detroit Tigers 6-3.
The win moved the White Sox within 3½ games of the first-place Tigers in the AL Central.
"I know they feel bad when they don't make a play and you try to pitch out of it. I try to pick them up," Buehrle said, adding that the victory in the opener of a three-game series is important but should be enjoyed with some perspective.
"We can't sit here and say 'Oh we're going to win the division now, we won the first game against these guys.' Obviously it's big to win first game, but it's a tough task tomorrow with (Justin) Verlander on the mound. They're one of the toughest lineups I've faced 1-9, these guys."
Buehrle (8-5) allowed 10 hits and Detroit had a runner on in each of his six innings, but the Tigers managed just two unearned runs off the left-hander.
"Buehrle's been like that all his life," Chicago manager Ozzie Guillen said. "You pick the mistake up and that's what Buehrle does. He got out there and regardless of what happens behind him, he continues to do what he does and never complain about anything."
Detroit rookie Duane Below (0-1) surrendered six hits and four runs in 4 2/3 innings.
Tigers manager Jim Leyland was ejected before the start of the sixth for questioning balls and strikes against Chicago's Alexei Ramirez, who had the first of the two, two-out hits in Chicago's three-run fifth.
"I thought we had Ramirez struck out and the umpire didn't think so. I told him that and he didn't appreciate that. I understand that, no big deal," Leyland said after his third ejection this season and 59th of his career. This one came from home plate umpire Jim Wolfe.
"I thought the pitch to Ramirez was a pitch that Jim was calling all night, really. Jim's a very good umpire."
Konerko hit his 23rd homer and Pierzynski his fourth for the White Sox, both off Chance Ruffin in his major league debut.
A gaffe by Cabrera at first base helped Chicago take the lead with a two-out, three-run rally in the fifth. Juan Pierre reached on a fielder's choice and was caught leaving early for second, but Cabrera dropped Below's throw to first. That allowed Pierre to reach second on the stolen base and he went on to score on Ramirez's two-out RBI single.
Konerko was walked intentionally and Adam Dunn walked to load the bases, ending Below's night. Quentin then greeted Ruffin, promoted from the minors earlier Monday, with a two-run double to make it 4-2.
"All year long we've been struggling with two outs and men in scoring position. And then all of a sudden we got that one," Guillen said of Ramirez's game-tying hit. "I think it pumps everybody up."
Chicago's defense came unglued in the second, leading to a pair of unearned runs for the Tigers. Magglio Ordonez singled with two outs and made it to third when White Sox second baseman Gordon Beckham dropped Cabrera's popup into shallow center for an error.
Victor Martinez added an RBI single before Jhonny Peralta hit another shallow pop to left center that Chicago center fielder Alex Rios let fall in front of him, thinking shortstop Ramirez was going to catch it. Detroit's second run scored on the play.
After an infield single loaded the bases, Rios went near the fence in center to track down Ryan Raburn's long drive to end the inning.
Chicago got a run in the bottom half on Konerko's sacrifice fly that followed singles by Brent Morel and Pierre and a sacrifice.
"Where we are at in the standings right now, it's like you know we are certainly not out of it but we would like to stick our nose in there a little bit further and start making up some ground," said Konerko, who also added two nice plays at first base.
"We've been treading water and teams have allowed us to tread water all year.
"It's time to make a move and get in there and make ourselves known in the division. It's still going to be another two months before there's an answer."
Buehrle improved to 18-9 in his career against the Tigers and to 7-1 in his last 11 starts against them. ... After Cabrera's homer in the seventh, Detroit had runners at first and second, but when Crain's low pitch bounced off catcher Pierzynski, the ball ricocheted to Crain, who threw to second to get Carlos Guillen for the final out. ... Detroit has captured 14 of the last 19 meetings with the White Sox. Chicago has won 3 of the last 4.