He has previously played in Major League Baseball (MLB) for the Minnesota Twins, Texas Rangers, Philadelphia Phillies, Baltimore Orioles, and St. Louis Cardinals.

[6][7][8] Despite worries that a stress fracture to his elbow would negatively impact his chances in the 2009 MLB Draft, the Minnesota Twins selected Gibson in the first round, 22nd overall after receiving the all-clear from the team's doctor.

[10] The stress fracture pushed Gibson's professional baseball debut back to the beginning of the 2010 season, when he was assigned to the Class A-Advanced Fort Myers Miracle of the Florida State League.

[12] Gibson's stint with the Miracle was short-lived: on May 11, he was promoted to the Double-A New Britain Rock Cats in order to clear room on the Fort Myers 25-man roster for new pitchers Loek van Mil and Andrei Lobanov.

[12] After winning his first three Double-A starts and building a strikeout-to-walk ratio of 3.17 in his first month and a half with his new team, Gibson was one of three Rock Cats players selected to appear at the 2010 Eastern League All-Star Game that July.

[13] Gibson put up a 7–5 record at New Britain, with a 3.68 ERA in 16 starts and 77 strikeouts in 93 innings, before he received another promotion to the Triple-A Rochester Red Wings on August 11.

Twins minor league director Jim Rantz informed reporters that there was no intention of promoting Gibson beyond Rochester during the 2010 season, as the team wanted to shut him down after 150–160 innings, and he had already pitched 136+1⁄3 between Fort Myers and New Britain.

[17] He was assigned to Rochester for the season, where he seemed to experience a sophomore slump: Gibson did not win a game for the Red Wings after May 29, and was 3–8 with a 4.81 ERA when he was placed on the disabled list at the start of August with an elbow injury.

[18] After a non-surgical rehabilitation program did not improve his health, Gibson underwent Tommy John surgery to repair his ulnar collateral ligament.

[21] He continued his rehabilitation process in the Arizona Fall League, where he finished 3–2 with a 5.40 ERA, striking out 28 batters and allowing 31 hits in 23+1⁄3 innings.

[23] The Twins called Gibson up to the major leagues on June 25, 2013, after starting pitcher Mike Pelfrey suffered a back injury that placed him on the disabled list.

At the time, he was the ninth pitcher to start a game for Minnesota during the 2013 MLB season, and his promotion offered a path to remain in the majors for the remainder of the year.

[27] He was shut down for the season on September 2, after pitching a combined 152+2⁄3 innings between Rochester and Minnesota, with the expectation that he would compete for a Twins starting rotation position the following spring.

[28] The Twins spent the 2013–14 offseason retooling their pitching rotation, spending approximately $84 million on signing new pitchers during the free agency period and giving Gibson an upwards battle for a major league position on opening day.

[30] He emerged as an early ace, posting an ERA of only 0.93 after his first three starts, including a scoreless eight-inning performance against the Toronto Blue Jays in 31 °F (−1 °C) weather.

[46] Because of his ulcerative colitis diagnosis, Gibson was considered "high risk" for COVID-19, and was given the option to opt out of the 2020 MLB season while receiving a full pro-rated salary.

[50] Gibson was tapped for his first career opening day start in 2021, where he was pulled after only one out after giving up five earned runs to the Kansas City Royals and briefly lifting his ERA to 135.00.

[51] His opening day outing proved to be a fluke, as Gibson's ERA over his next five starts was only 0.82, and he did not allow a single home run in the month of April.

[52] After leading the AL with a 1.98 ERA and a 6–0 record through his first 16 starts, Gibson received his first All-Star Game selection in 2021, joining his Rangers teammates Joey Gallo and Adolis Garcia.

[54] On July 30, 2021, Gibson was traded to the Philadelphia Phillies along with Ian Kennedy, Hans Crouse, and cash considerations in exchange for Spencer Howard, Kevin Gowdy, and Josh Gessner.

[62] This expanded repertoire has made Gibson an unpredictable pitcher to face; whereas, early in his career, batters knew how to hit well against him, he has improved at generating strikeouts, particularly with use of his slider.