He has previously played in MLB for the San Diego Padres and Texas Rangers, and in Nippon Professional Baseball (NPB) for the Yomiuri Giants.

He was an All-Star in 2018, led the National League in wins that season, and finished sixth in NL Cy Young Award voting that year.

Mikolas pitched for Jupiter Community High School in Palm Beach County, Florida, from which he graduated in 2006.

The San Diego Padres selected Mikolas in the seventh round of the 2009 Major League Baseball draft.

[5] He began 2011 with the High-A Lake Elsinore Storm and, after going 3–0 with 12 saves (4th in the California League) and a 1.13 ERA in 34 games,[4] was promoted to the Double-A San Antonio Missions on July 4.

[9] Mikolas was sent down to the Triple-A Tucson Padres on June 5, after making 13 appearances and allowing five earned runs in 132⁄3 innings.

The Padres traded Mikolas to the Pittsburgh Pirates, along with Jaff Decker, for Alex Dickerson after the 2013 season.

Mikolas started his first career game against the Baltimore Orioles,[18] giving up three hits and three runs in 5+1⁄3 innings.

[19] On November 25, 2014, Mikolas signed a one-year, US$700,000 deal with the Yomiuri Giants of Nippon Professional Baseball for the 2015 season.

[24] Mikolas threw his first major league complete game, a shutout, on May 21, 2018, at Busch Stadium against the Kansas City Royals.

[32] He missed the entire 2020 season due to undergoing surgery to repair a flexor tendon in his right arm.

[33] On August 20, 2021, Mikolas was activated off of the 60-day injured list after missing the past 75 games with a right forearm strain.

[35] Mikolas was named to the 2022 Major League Baseball All-Star Game after replacing Corbin Burnes.