[1] While in high school, he developed a baseball rivalry and eventual friendship with Patrick Mahomes[2] He committed to attend the University of Arizona.

[6] On July 16, he was suspended without pay for 50 games after testing positive for Oxilofrine, which is a banned substance under the Minor League Drug Prevention and Treatment Program.

[11] He posted a 2.08 ERA and gave only 29 walks, striking out double-digit batters in four of his last six starts, including a career-high 11 twice.

[15] After the season, he played for the Surprise Saguaros in the Arizona Fall League, making six starts and allowing five runs in 22+1⁄3 innings for a 2.01 ERA.

[16] In an offseason workout on January 17, 2017, throwing from flat ground with run-up, Kopech threw a pitch that was unofficially clocked at 110 miles per hour (180 km/h) with a 3-ounce (85 g) ball.

[19] On August 18, 2017, the White Sox promoted Kopech to the Triple-A Charlotte Knights after he posted a 2.87 ERA over 119+1⁄3 innings in 22 starts with 155 strikeouts.

[5] The White Sox promoted him to the major leagues on August 21, and he made his debut that day against the Minnesota Twins.

[22] He made a total of four starts, with a 1–1 record and 5.02 ERA[23] before undergoing Tommy John surgery on September 18, putting him out for the rest of the 2018 season plus all of 2019 as well.

[26] On May 26, Kopech threw a pitch and then slipped and fell off the mound leading to his being placed on the injured list with a strained left hamstring.

[31] He suffered a left knee strain against the Kansas City Royals on August 23[32] After he returned, he made two more starts before he was placed on the injured list again on September 17 with right shoulder inflammation, shutting him down for the season.

[34] On January 13, 2023, Kopech agreed to a one-year, $2.05 million contract with the White Sox, avoiding salary arbitration.

[38] On July 10, he became the second White Sox pitcher to throw an immaculate inning and the first since Sloppy Thurston in 1923 while recording a save against the Twins.

[23] On July 29, 2024, the White Sox traded Kopech to the Los Angeles Dodgers as part of a three-team deal that also sent Tommy Edman and Oliver Gonzalez to Los Angeles, sent Erick Fedde and Tommy Pham to the St. Louis Cardinals, and sent Miguel Vargas, Alexander Albertus, and Jeral Pérez to the White Sox.

[45] In May 2022, he took a brief paternity leave from the White Sox while he attended the birth of his second child, by his new girlfriend,[46] fitness instructor Morgan Eudy.