As a freshman in 2013, he made 9 starts and appeared in 16 games. He had a 4–3 record with a 3.14 earned run average (ERA) and 57 strikeouts. As a sophomore, he went 12–2 with 111 strikeouts and a 2.64 ERA and was a member of the 2014 College World Series championship team. On June 16, 2014, Buehler pitched 5.1 innings of no-hit relief, retiring the first nine batters he faced and striking out 7 batters in Vanderbilt’s 6-4 win over University of California Irvine.

After the 2014 season Buehler played for Team USA and the Yarmouth–Dennis Red Sox of the Cape Cod Baseball League (CCBL). He posted a 0.63 earned run average with 24 strikeouts over 28.2 innings pitched for the Red Sox. In the 2014 CCBL playoffs, he did not allow a run in 15.1 innings, won both of his starts, and was a co-winner of MVP honors, leading the Red Sox to the league championship.

In 2015, as a junior he posted a 2.97 ERA in 78.2 innings for the Commodores while striking out 81 and walking 25. Over the course of his three-year college career, he went 20-7 with a 2.88 ERA in 49 games, striking out 249 against only 83 walks.

Buehler was selected by the Los Angeles Dodgers with the 24th overall selection of the 2015 Major League Baseball draft and signed on July 17, 2015, for a $1.78 million bonus. Soon after his signing, it was revealed that he would require Tommy John surgery and would therefore be sidelined for a year and a half with recovery. He finally made his professional baseball debut on August 23, 2016 for the Arizona League Dodgers, striking out three and retiring all six batters he faced. He was then promoted to the Great Lakes Loons of the Midwest League on August 28. He appeared in two games for the Loons, making one start, and did not allow a run or a hit in the three innings he pitched.

The Dodgers added Buehler to the major league roster for the first time on September 6, 2017, and he made his major league debut that night with two scoreless innings of relief against the Colorado Rockies. His first MLB strikeout was against Charlie Blackmon of the Rockies. He picked up his first major league win with a scoreless inning of relief against the Philadelphia Phillies on September 21. Overall, Buehler appeared in eight Dodgers games in 2017, allowing eight runs in 9⁄3 innings (7.71 ERA) with 12 strikeouts and eight walks.

Buehler made his first major league start on April 23, 2018, against the Miami Marlins, pitching five scoreless innings. On May 4, against the San Diego Padres, he took a no-hitter through six innings, with eight strikeouts, until being taken out of the game after 93 pitches. Three relief pitchers combined to finish it off as the Dodgers won 4–0, the first combined no-hitter in franchise history. He was placed on the disabled list on June 21 because of a rib injury. He returned to make an appearance out of the bullpen on June 28 but allowed five earned runs in one inning before returning to the disabled list. On July 13, Buehler made his first start in over a month against the Los Angeles Angels, allowing two solo home runs to Kole Calhoun but no other earned runs. He set a new career high in strikeouts with nine on August 22. After three more nine-strikeout starts, he struck out 12 on September 19 against the Colorado Rockies.

On October 1, Buehler started the NL West Tie-Breaker Game against the Colorado Rockies. He picked up the win, giving up only one hit and allowing no runner to advance past second base. He also got his first career MLB run batted in in his 47th plate appearance. In 24 appearances for the Dodgers (23 starts and one relief appearance) in 2018, Buehler was 8–5 with a 2.62 ERA and 151 strikeouts. In the 2018 NLDS against the Atlanta Braves, he started one game and allowed five runs in five innings; in the 2018 NLCS against the Milwaukee Brewers he started two games, allowing five runs in 11⁄3 innings; and he threw seven scoreless innings in Game 3 of the 2018 World Series against the Boston Red Sox. Buehler finished third in voting for the National League Rookie of the Year, behind Atlanta Braves outfielder Ronald Acuña Jr. and Washington Nationals outfielder Juan Soto.

Buehler is a native of Lexington, Kentucky, the “Horse Capital of the World”, home to the Kentucky Horse Park, The Red Mile and Keeneland race courses, and grew up a big fan of horse racing. He has a minority ownership stake in 2020 Kentucky Derby and 2020 Breeders’ Cup Classic winner Authentic, trained by Bob Baffert. Buehler attended the 2020 Breeders’ Cup Classic to see Authentic win at Keeneland.