The San Diego Padres selected Mikolas in the seventh round of the 2009 Major League Baseball draft. Mikolas pitched as a reliever for the Class-A Fort Wayne TinCaps in 2010, and was 6–3 with 13 saves and posted a 2.20 earned run average in 60 games. He was named a Midwest LeagueAll Star. He began 2011 with the High-A Lake Elsinore Storm and, after going 3–0 with 12 saves and a 1.13 ERA in 34 games, was promoted to the Double-A San Antonio Missions on July 4. Mikolas finished out 2011 by going 1–0 with nine saves and compiling a 1.67 ERA as a reliever for the Missions over 28 games. Mikolas received a non-roster invitation to spring training in 2012. He was assigned to the minor league camp later in the spring, and started the year with San Antonio. Mikolas was called up to the majors for the first time directly from Double-A San Antonio on May 5, 2012. He made his debut at Petco Park against the Miami Marlins, for whom he grew up rooting. The first batter he faced, Giancarlo Stanton, hit a home run. Mikolas was sent down to the Triple-A Tucson Padres on June 5, after making 13 appearances and allowing five earned runs in 13 innings. He was recalled on July 5, and made two more appearances before being optioned back to Triple-A. He was recalled from Tucson again on August 5, and stayed with the big league club through the rest of the year. For the season, Mikolas was 2–1 and amassed a 3.62 ERA and 23 strikeouts versus 15 walks over 32 innings. In 2013 with Tucson, he was 4–2 with a 3.25 ERA, and 26 saves. He pitched scoreless innings for the Padres. Mikolas was designated for assignment by the Padres on November 20, 2013.
Texas Rangers
The Padres traded Mikolas to the Pittsburgh Pirates, along with Jaff Decker, for Alex Dickerson after the 2013 season. During that offseason, the Pirates traded him to the Texas Rangers in exchange for Chris McGuiness. He began the 2014 season with the Round Rock Express. Mikolas was called up to the Rangers' 25-man roster on July 1, 2014. In innings pitched prior to his promotion, he had a 5–1 win–loss record with a 3.22 ERA. Mikolas started his first career game against the Baltimore Orioles, giving up three hits and three runs in innings. He spent the remainder of the season with Texas, going 2–5 with a 6.44 ERA in ten starts. The Rangers released Mikolas after the 2014 season.
Yomiuri Giants
On November 25, 2014, Mikolas signed a one-year, deal with the Yomiuri Giants of Nippon Professional Baseball for the 2015 season. In 2015, he was 13–3. After the season, the Giants re-signed him to a two-year deal. In three seasons for Yomiuri, he pitched to a 31–13 record with a 2.18 ERA in 62 starts.
St. Louis Cardinals
Mikolas signed a two-year, $15.5 million contract with the St. Louis Cardinals on December 5, 2017. He won his debut with the Cardinals 8–4 on April 2, 2018, at Miller Park against the Milwaukee Brewers. While batting, he hit a two-run home run versus Zach Davies for his first major league hit. On the mound, he completed innings, allowing three home runs and four runs total, while striking out five and walking none. Mikolas threw his first major league complete game, a shutout, on May 21, 2018, at Busch Stadium against the Kansas City Royals. He struck out nine, walked one, and gave up only four hits as the Cardinals defeated Kansas City 6–0. Owning a 9–3 record, a 2.63 ERA, and a 1.03 WHIP, Mikolas was named to the 2018 Major League Baseball All-Star Game, his first All-Star selection. Mikolas finished his 2018 campaign with an 18–4 record, a league-leading.818 won-loss percentage, a 2.83 ERA, 1.071 WHIP, walking just 29 batters in innings, in 32 starts. His 18 wins were tops in the NL. He led the majors with only 1.30 BB/9, and also led all major league pitchers in first-strike percentage. In addition, he had the highest zone percentage of all major league pitchers, with 48.0% of his pitches being in the strike zone. On defense, he was second among NL pitchers in range factor/9 innings, 3rd in putouts, and 4th in assists. He came in sixth in the voting for the 2018 NL Cy Young Award. On February 26, 2019, Mikolas and the Cardinals agreed on a four-year extension worth $68 million. He finished the 2019 regular season with a 9–14 record and a 4.16 ERA, striking out 144 over 184 innings. He was named St. Louis' Game 1 starter for the 2019 National League Division Series. On July 28, 2020, he was declared out for the season without appearing in a game due to undergoing surgery to repair a flexor tendon in his right arm.
Personal life
Mikolas earned the nickname "Lizard King" when, on a bet, he ate a lizard in the bullpen during a 2011 Arizona Fall League game. The video of Mikolas eating the lizard was posted to YouTube. Mikolas is married to Lauren Mikolas, who was an elementary school teacher, UFCring girl, and certified wellness coach who became a social media celebrity in Japan with her lifestyle blog. Their first child, a daughter, was born in March 2017, and his wife gave birth to twins in July 2018.
