He has previously played in Major League Baseball (MLB) for the Houston Astros, Atlanta Braves, Chicago White Sox, Arizona Diamondbacks, Texas Rangers, Minnesota Twins, and Milwaukee Brewers.

He played for the Atlanta Braves in 2019 and signed a three-year contract with the Chicago White Sox before the 2020 season.

Keuchel attended Bishop Kelley High School in Tulsa, Oklahoma, where he led the baseball team to the state championship.

The final regular season series was against Drew Pomeranz and #9 Ole Miss at Baum Stadium.

[7] After his junior year at Arkansas, the Houston Astros selected Keuchel in the seventh round of the 2009 Major League Baseball (MLB) draft.

[10] Keuchel finished the 2012 season with a 5.27 ERA in 16 games started, while allowing more walks (39) than strikeouts (38).

[19] He won his third AL Pitcher of the Month Award for August, after pitching to a 4–1 record and a 1.94 ERA in six starts.

Prior to Keuchel, rotations mates Dave Ferriss and Tex Hughson shared the record while with the 1946 Boston Red Sox, each going 13–0 at Fenway Park.

[25] Keuchel started and won the AL Wild Card Game versus the New York Yankees on three days' rest.

In 2016, Keuchel won another Gold Glove Award, but he went 9–12 with a 4.55 ERA and a 1.286 WHIP in 26 games pitched and 168 innings.

[33] Keuchel began the 2017 season by winning his fourth career AL Pitcher of the Month Award in April, after posting a 5–0 W–L and 1.21 ERA over six starts.

[34] He proceeded to start the season with a 7–0 record and a 1.84 ERA; however, on May 20, 2017, he was placed on the 10-day disabled list due to a pinched nerve in his neck.

The Astros won the American League West division with a 101–61 record to reach the postseason for the second time in three seasons.

In the 2017 American League Division Series, the Astros faced the Boston Red Sox, and Keuchel started Game 2.

He pitched 5+2⁄3 innings while allowing one run on three hits with seven strikeouts as Houston won 8–2 before winning the series two games later.

[40] Keuchel started Game 1 of the 2017 American League Championship Series against the New York Yankees, which resulted in seven scoreless innings while allowing just four hits with ten strikeouts in a 2–1 victory.

[41] He started Game 5 five days later, but he lasted just 4+2⁄3 innings while allowing four runs on seven hits in a 5–0 loss.

[42] However, the Astros won the pennant a couple of days later to advance to their first World Series in twelve years.

In the 2017 World Series, Keuchel was tapped to start Game 1; he allowed three runs on six hits in 6+2⁄3 innings of work that saw him take the loss in a 3–1 result.

On December 30, 2019, the Chicago White Sox signed Keuchel to a three-year, $55.5 million contract.

[53] He made his White Sox debut on July 25, 2020, picking up a win over the Minnesota Twins.

[67] Keuchel made his Rangers debut on August 27, giving up 7 earned runs over 5.1 innings pitched in a blowout 11–2 loss to the Detroit Tigers.

[69] On June 22, 2023, Keuchel signed a minor league contract with the Minnesota Twins organization.

On August 1, Keuchel exercised a second opt–out in his deal,[73] and was selected to the major league roster two days later following an injury to Joe Ryan.

[74] On August 6, Keuchel made his debut with Minnesota, going five innings allowing eight hits, two walks, and one earned run.

After signing with the White Sox, Keuchel purchased a $2 million home in the Lake View neighborhood of Chicago.