Records and statistics

On April 16, 2005, he finished a game against the Seattle Mariners in only 1 hour and 39 minutes, giving up only 1 run and 3 hits (all to Ichiro Suzuki), and backed by only two White Sox runs, both homers by Paul Konerko. In the game, he threw just 106 pitches. Subtracting the time spent between innings, the game took only 63½ minutes to play.

On October 25, 2005, Buehrle became the first pitcher in World Series history to start and save consecutive games.

On May 14, 2006, in a game against the Minnesota Twins, Buehrle became the first major league starting pitcher in over a century to allow seven runs in the first inning but then win the game. The previous time had been on September 29, 1900, when Jack Powell of the St. Louis Cardinals pitched such a game against the Chicago Orphans.

Buehrle hit his first major league home run on June 14, 2009 off Milwaukee Brewers starting pitcher Braden Looper, becoming the first White Sox pitcher to hit a home run in a game since Jon Garland on June 18, 2006, at Cincinnati. Buehrle ripped a 3-2 pitch off Looper well over the fence in right center to lead off the top of the third inning. He then took a normal trot around the bases and was greeted briefly by his teammates at home plate before running down the dugout tunnel.

On July 23, 2009, Buehrle threw his second career no-hitter against the Tampa Bay Rays at U.S. Cellular Field. It was also the eighteenth perfect game in Major League history. With this perfect game, Buehrle became the 24th pitcher to throw multiple no-hitters in a career. Coincidentally, the home plate umpire for both of Buehrle's feats were Eric Cooper.