Buehrle flawlessly pitched the White Sox into a share of first place in the American League Central in impeccable style with the 18th perfect game in major-league history.
When shortstop Alexei Ramirez threw to first baseman Josh Fields to retire Jason Bartlett for the final out, Buehrle completed the latest achievement in his impressive career with a 5-0 victory over defending AL champion Tampa Bay before 28,036 energized fans at U.S. Cellular Field.
"I never thought I'd throw a no-hitter, never thought I'd throw a perfect game and I never thought I'd hit a home run," Buehrle said. "Never say never in this game because crazy stuff can happen."
Buehrle, 30, a four-time All-Star, became just the sixth pitcher in big-league history to throw a perfect game and another no-hitter. He pitched a no-hitter against Texas in 2007, and he hit a home run in Milwaukee last month.
Thursday's achievement marked the 17th no-hitter in Sox history and only the second perfect game. Charles Robertson had the other at Detroit on April 30, 1922.
Buehrle (11-3) joined Frank Smith (1905, 1908) as the only Sox pitchers to throw two no-hitters.
Buehrle's perfection couldn't have arrived at a more opportune time for the Sox, who moved into a share of first place for the first time since May 1 as they open a four-game series Friday at co-leader Detroit.
Since losing to the Tigers in the first game of a June 8 doubleheader that infuriated manager Ozzie Guillen, the Sox have posted a 24-14 record, erasing a 5 1/2 -game deficit.
"The perfect game is the story, but the fact that we won the game, won the series against Tampa Bay and go into Detroit with some momentum ... that hopefully will carry into this weekend," said catcher A.J. Pierzynski, who rested as Ramon Castro, 33, handled the game.
Fields was the hitting hero, giving Buehrle the only run support he needed on a grand slam in the second inning off Scott Kazmir. Dewayne Wise provided the fielding highlight, robbing Gabe Kapler of a home run for the first out in the ninth inning.
What made this perfect game so remarkable for Buehrle is that he relied on his breaking ball and off-speed pitches.
"One of the toughest things I've seen in my life is to see Buehrle throw a no-hitter," Guillen said. "Not because he can't, it's because his game plan is to make sure those guys put the ball in play and ... get out of there as quickly as he can.
"I was talking to his wife [Jamie] right after the game, and I said, 'Whenever I think he can't do something, he always do it.' It's amazing. We're excited. In the coaches' room, everybody was in tears."
Jamie Buehrle said she was trying "not to throw up" in the ninth inning because of nerves. Then Wise preserved history with the best catch of his career.
Wise, inserted in center field for defensive purposes, sprinted to left-center field in a desperate effort to catch Kapler's drive.
He leaped above the fence to make the catch and momentarily lost control of the ball before grabbing it for the first out and falling to the ground.
"It was a special moment for Buehrle and Wise," Kapler said. "They earned it."
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More insidePhil Rogers and Steve Rosenbloom; plus a batter-by-batter breakdown and a look at Wise's catch. PAGES 5-7