In the ninth, his perfect game was almost in jeopardy. But center fielder Dewayne Wise sprinted toward the fence to keep Buehrle on track for his second no-hitter and the 18th perfect game in Major League history, as well as the White Sox 5-0 victory.
Afterward, President Barack Obama, who was on Air Force One, called Buehrle to congratulate him just before arriving in Chicago.
"I spoke to Buehrle on the phone on the Air Force One. That's one of the privileges of being president," said Obama.
It's just the second perfect game in Sox history and the first to happen in Chicago.
White Sox fans who watched it happen celebrated long after the final out.
"Sixty-four years I've been coming out here, never seen anything like this. Even if they live to be my age, they'll probably never see anything like this," said fan Stan Hrycak, who was there with two kids.
White Sox fans poured out of U.S. Cellular Field, excited about only the 18th perfect game in MLB history.
"I have never seen anything better than this. I will never see anything better than this, best game I've ever been to," said one fan.
"Awesome, never felt that experience before," said one young fan.
PHOTO GALLERY: More pictures from The Associated Press.
Buehrle's performance has some fans calling it the birth of a new Sox season.
"Just like a fantasy world I'm living right now, just incredible," said Sox fan Wally Skwarek.
As fans like Skwarek grabbed breakfast Friday morning, they were focused on the morning paper cover stories, the magic moments of Buehrle's perfect game. Even one Cubs fan in Bridgeport couldn't help herself.
"Well, my son is [a Sox fan] so we the divide our loyalties, but yeah, we'll watch some more of the games," said Sue Clemons, Cubs fan.
"In the middle of the sixth, I looked at the scoreboard and thought about it, then tried wipe my thoughts clear because I didn't want to jinx them," said fan Mike Goldston.
"The final catch when they caught that ball, that was it," said Tony Dinos, fan.
"You don't have to be a Sox fan to get caught up in the Buehrle buzz," said an ESPN radio host.
On ESPN radio Friday morning, the callers and hosts couldn't get enough of the game. It's just the second perfect one ever for the Sox, the first one was in 1922. The hosts think that Thursday's perfection may drive momentum.
"I haven't felt a White Sox like this since back when they won the series in 2005. They are the center of the baseball world and led by such a great guy like Mark Buehrle, and it's such an amazing accomplishment and feat for the team," said Jeff Dickerson, ESPN AM 1000.
The Sox play a double-header against Detroit Friday.
While mixing curves and changeups, the chatty veteran was throwing an old baseball superstition aside and having a grand old time -- just as he did the last time he pitched a no-hitter.
Only this time, he was perfect.
"I don't think it's really soaked in," he said. "I think it'll soak in a little later. Obviously, anytime your name gets up there with some of the greats in the game, that means a lot. I think it's a thing when you retire and sit back and see how many perfect games have been thrown -- and your name's in there -- I think I'm going to sit back and be surprised."
Along with the perfect pitches, he'll probably think about Wise's perfect play.
The image of Wise, just in as a defensive replacement, sprinting toward the fence in left-center after the ball jumped off Gabe Kapler's bat leading off the ninth will be tough to forget.
Wise jumped and extended his right arm above the top of the 8-foot wall. The ball landed in his glove, then popped out for a split second as he was caroming off the wall and stumbling on the warning track. Wise grabbed it with his bare left hand, fell to the ground and rolled. He bounced up, proudly displaying the ball for the crowd.
A home run turned into an out, and with his biggest scare behind him, Buehrle finished off the perfect game.
"I was with the Braves in '04 and I was there when Randy Johnson of the Diamondbacks pitched a perfect game. So I've been on both sides of it," Wise said. "It was probably the best catch I've ever made because of the circumstances.
"It was kind of crazy, man, because when I jumped, the ball hit my glove at the same time I was hitting the wall. So I didn't realize I had caught it until I fell down and the ball was coming out of my glove, so I reached out and grabbed it."
Kapler called it "magical for both Wise and Buehrle, and most guys earn those moments."
White Sox manager Ozzie Guillen was happy he made the switch to Wise, who came in for Scott Podsednik.
"I guess that's our job," Guillen said.
And as he made the perfect push toward history, Buehrle simply wouldn't leave his antsy teammates alone. He kept talking to them, and even hit rookie Gordon Beckham with this question in the seventh: "You think I'm going to do it?"
"I just looked down and didn't say anything because I didn't want to jinx it," Beckham said.
In the fifth inning, Buehrle went back to the clubhouse and told everyday catcher A.J. Pierzynski -- who had the day off -- to go watch in the dugout and enjoy himself.
"People say you can jinx it, but not Mark," Pierzynski said. "He's all about having fun."
Buehrle was having plenty of it before the game, when he kept reminding Pierzynski about his no-hitter against Texas two years ago.
So Pierzynski told him: "'Go out and throw a perfect game, then.' And he said: 'I just might."
With fans chanting Buehrle's name, Jason Bartlett got ahead 2-1, then grounded to shortstop Alexei Ramirez, who threw to first baseman Josh Fields. Buehrle put both hands on his head and was mobbed by teammates between the mound and first base.
"Never thought I'd throw a no-hitter, never thought I'd throw a perfect game, never thought I'd hit a home run," said Buehrle, who has done all three. "Never say never in this game because crazy stuff can happen."
It was the 16th perfect game since the modern era began in 1900 and the first since Johnson's on May 18, 2004.
"We joked around, a 30-second phone call, and I'm like 'What? That's all he's got for me?"' Buehrle said of President Obama's phone call.
Obama, a lefty like Buehrle, wore a White Sox jacket when he threw out the ceremonial first pitch at last week's All-Star game in St. Louis.
"I told him how surprised I was that he actually did it," Buehrle said. "He said, 'Congratulations, and it's an honor. A lot of people are going to remember this forever."'
Obama had spoken with Buehrle -- a St. Charles, Mo., native -- in the AL clubhouse last week.
"As a fan, it's extraordinary," White House press secretary Robert Gibbs quoted Obama as saying. "When you're a White Sox fan and know the guy who did it, it makes it even more fun."
Buehrle (11-3) had the best time of all.
Backed by Fields' second-inning grand slam, Buehrle helped Chicago move within a percentage point of AL Central-leading Detroit.
In a 6-0 win over Texas on April 18, 2007, Buehrle also faced the minimum 27 batters. He walked Sammy Sosa in the fifth inning of that game, then picked him off two pitches later.
"I bought everyone watches after the last one. That was an expensive no-hitter," Buehrle said. "This one will probably be more expensive."
NOTE: Home plate umpire Eric Cooper was also behind the plate for Buehrle's no-hitter two years ago.
The Associated Press contributed to this report.