Cole played for the baseball team at Orange Lutheran High School and was selected by the Yankees in the first round of the 2008 MLB Draft.

He gained national attention while pitching for the varsity team in his junior year, as his fastball reached 94 miles per hour (151 km/h).

[3] He reached 96 miles per hour (154 km/h) in a showcase for the best prep school talents, and close to 50 scouts attended the first game of his senior season.

The Yankees were reportedly planning on offering Cole a $4 million signing bonus, which was above the recommended amount for the slot.

John Savage, coach of the UCLA Bruins, made Cole the team's Friday night starting pitcher in his freshman year.

[25] In twelve starts with the Curve, Cole pitched to a 2.90 ERA, before the Pirates promoted him to the Indianapolis Indians of the Class AAA International League on August 29, 2012.

[28] Due to injuries to James McDonald and Wandy Rodríguez, the Pirates promoted Cole to the major leagues, to make his MLB debut on June 11, 2013.

Cole pitched 6+1⁄3 innings being charged with two earned runs and got the win as the Pirates won over the San Francisco Giants, 8–2.

[30] He was the fifth pitcher for any team to accomplish the feat in the past 40 years, joining Rich Gale of the 1978 Royals, Kaz Ishii of the 2002 Dodgers, Jered Weaver of the 2006 Angels and Scott Lewis of the 2008 Indians.

Cole started Game Two of the 2013 National League Division Series, going six innings allowing two hits, one earned run, and five strikeouts, and ultimately defeating the St. Louis Cardinals.

[33] After focusing on his fastball during his rookie season, Cole entered 2014 spring training working on improving his curveball and slider.

[37] On September 7, 2014, Cole hit his first career home run at Wrigley Field off of Chicago Cubs pitcher Blake Parker.

[38] On September 23, Cole helped the Pirates clinch a second consecutive playoff berth by beating Alex Wood and the Atlanta Braves.

[40] He was the Pirates' choice to start the 2015 National League Wild Card Game against the Chicago Cubs but took the loss after giving up four earned runs on six hits and a walk in five innings pitched.

[43] On January 13, 2018, the Pirates traded Cole to the Houston Astros for Joe Musgrove, Michael Feliz, Colin Moran and Jason Martin.

[44] On April 29, 2018, Cole struck out 12 hitters in a game against the Oakland Athletics that resulted in a no-decision but an Astros win.

[45] On May 4, against the Arizona Diamondbacks Cole struck out 16, allowed only one hit, and pitched his first career shutout as the Astros won 8–0.

[48] In Game 2 of the 2018 American League Division Series against the Cleveland Indians, Cole struck out 12 and walked none in seven innings in a 3–1 victory.

Cole became the second pitcher to strike out at least 12 hitters with no walks in the postseason, after Tom Seaver in the 1973 National League Championship Series.

[51] The following start, September 24, 2019, Cole struck out 14 batters to break the single-season strikeout record for any Astros pitcher, bringing his total to 316 on the year, and allowing only two singles in his appearance of seven scoreless innings.

[62] On July 23, 2020, Cole made his Yankees debut as an Opening Day starting pitcher throwing 5 innings against the Washington Nationals and allowing just one hit, a home run by Adam Eaton.

On May 12, 2021, Cole notched his 1,500th career strikeout, becoming the second-fastest pitcher in history to reach the milestone behind Randy Johnson.

Cole was named the AL Pitcher of the Month in April after winning five of six starts and allowing only 5 runs in 40.2 innings pitched.

He also became the third-fastest pitcher in MLB history (1,714.2 fewest innings) to reach accomplish this feat, just behind Chris Sale (1,626) and Pedro Martinez (1,711.1).

[77] On September 27, against the Blue Jays, Cole pitched a complete game shutout in his final start of the 2023 season.

[88] Cole appeared in the World Series for the second time in his career, pitching in Games 1 and 5 against the Los Angeles Dodgers but receiving a no-decision in each.

He will remain with the team on a four-year, $144 million contract he opted out of two days prior, although extension talks with him and the Yankees will continue.

[92] Cole is a power pitcher who features a four-seam and two-seam fastball that he regularly throws around 97 mph,[93] but has been clocked as high as 102 miles per hour (164 km/h) in college.

[95] Between 2017 and 2018, due to his increased spin rate and a more complete arm deceleration and follow-through, his fastball got a lower WHIP, and used his sinker less often, no longer "pitching to contact".

[97] In the first round of 2019 ALDS, his strikeout pitches were high fastballs, sliders and knuckle curveballs which curve down and away from right-handed batters.