Pettitte won the 2001 AL Championship Series Most Valuable Player (MVP) Award in helping his team win the pennant.

Pettitte's second tenure with the team lasted six seasons, interrupted by a one-year retirement in 2011, and also produced a fifth World Series championship in 2009.

[5] As Pettitte enrolled in a junior college rather than a four-year school, the Yankees retained the right to sign him as a draft-and-follow prospect.

[8] Pettitte pitched for the Prince William Cannons of the Class A-Advanced Carolina League in the 1993 season, finishing the year with an 11–9 record, a 3.04 ERA, 129 strikeouts, and 47 walks in 26 starts.

[9] Pettitte began the 1994 season with Albany-Colonie, where he had a 7–2 record and 2.71 ERA in 11 starts, before receiving a promotion to the Columbus Clippers of the Class AAA International League.

Hitchcock won the competition, and Pettitte opened the season in the bullpen,[4] making his major league debut with the Yankees on April 29, 1995.

[13] Pettitte won six of his last seven starts, finishing the season with a 12–9 record and a 4.17 ERA, and placed third in American League (AL) Rookie of the Year Award balloting, behind Marty Cordova and Garret Anderson.

[14] He started Game 2 of the 1995 American League Division Series (ALDS) against the Seattle Mariners, allowing four runs in seven innings.

[19] The Yankees defeated the Texas Rangers in the 1996 ALDS[20] and the Baltimore Orioles in the 1996 American League Championship Series (ALCS).

The best offer actually came from the Boston Red Sox, the historic rivals of the Yankees, at four years for $52 million, yet Pettitte never seriously considered signing with them.

[34] His 2004 season, in which he held batters to a .226 batting average, was shortened by elbow surgery to repair a torn flexor tendon.

[42] In 2007, he led the American League in starts (34), was seventh in batters faced (916), and was ninth in innings pitched (215+1⁄3), finishing the regular season with a 15–9 win–loss record.

Pettitte began the 2009 season as the Yankees' fourth starter, behind CC Sabathia, A. J. Burnett, and Chien-Ming Wang, followed by Joba Chamberlain.

This brought his career total of series-clinching wins to five, breaking the record he previously shared with Roger Clemens, Catfish Hunter and Dave Stewart.

[48] Pettitte drove in his first postseason run during Game 3 of the World Series when he got a single to center field that scored Nick Swisher.

Experts were critical of the decision to pitch the 37-year-old on short rest,[50][51] but Pettitte again was the winning pitcher in Game 6, defeating the Philadelphia Phillies 7–3.

[55] In the first half of the 2010 season, Pettitte went 11–2 with a 2.70 ERA, earning an appearance in the 2010 Major League Baseball All-Star Game.

Stating that his return gave him "the itch", Pettitte signed a minor league contract with the Yankees worth $2.5 million on March 16, 2012.

[67] On July 1, in a game against the Minnesota Twins, Pettitte struck out Justin Morneau, thereby passing Whitey Ford as the Yankees all-time strikeout leader with 1,958.

In 2009, he became the second pitcher in history to win three series-clinching games (ALDS, ALCS and World Series) in the same postseason (following Derek Lowe in 2004).

[83] Pettitte played in eight different World Series (seven with the Yankees, and one with the Astros), and been on the winning end of 19 postseason series—both of which were tops among active players.

On September 30, 2006, the Los Angeles Times reported that former relief pitcher Jason Grimsley, during a raid by federal agents investigating steroids in baseball on June 6, 2006, named Pettitte as a user of performance-enhancing drugs.

[88] Grimsley had told investigators that he got amphetamines, anabolic steroids, and human growth hormone (HGH) from someone (later named as Kirk Radomski) recommended to him by former Yankees trainer Brian McNamee, who is a personal strength coach for Roger Clemens and Pettitte.

"[89] Contrary to the initial Los Angeles Times report, neither the name of Clemens nor Pettitte appeared in the affidavit submitted by Grimsley.

[91] Pettitte verified McNamee's claim, admitting to using the HGH on two occasions in 2002, as it was meant to help heal an injury, and not to enhance his performance.

In the press conference, he said the performance-enhancing-drug scandal has put a "strain" on his relationship with Clemens, his close friend and former teammate.

[94] Pettitte threw a four-seam fastball, a cutter, a curveball, a sinker, a changeup to right-handed batters, and a slider.

[98] The family resides in Houston, although Pettitte also owned a home in Westchester County, New York before putting it up for sale in 2020.

Josh was selected by the Yankees in the 37th round of the 2013 MLB draft, but enrolled at Baylor University rather than sign a professional contract.

[101] He played at Rice University after transferring from Baylor in April 2014, before announcing his retirement on Instagram after a series of injuries in February 2018.