Maeda was selected out of PL Gakuen Senior High School by the Hiroshima Toyo Carp of Japan’s 2006 NPB Draft (NPB). He played in 2007 for the Carp’s secondary team, before being called up to the NPB team in 2008. In his rookie season of 2008, Maeda posted a 9–2 win-loss record with a 3.20 earned run average (ERA) in 19 games (18 starts). In 2009, he was 8–14 with a 3.36 ERA in 29 starts. In 2010, he performed even better with a 15–8 record, a 2.21 ERA, and 174 strikeouts in 28 starts. In 2011, his record was 10–12 while having a 2.46 ERA and 178 strikeouts in 31 starts. The 2012 season became far better for Maeda as his record was 14–7 with a 1.53 ERA in 29 starts. In 2013, his record was 15–7 with a 2.10 ERA in 26 starts. In 2014, he went 11–9 with a 2.60 ERA in 27 starts. In 2015, he went 15–8 with a 2.09 ERA in 29 starts. He won the Sawamura Award as the league’s best pitcher in both 2010 and 2015 and was the youngest pitcher in Japanese baseball history to achieve the pitching Triple Crown. The Carp chose to make him available to Major League Baseball (MLB) teams through the posting system in December 2015.

In the 2013 World Baseball Classic, and said he would use the tournament to assess his desire to compete in MLB, based on how he fared against their hitters. Maeda started two games in the pool rounds, against China and Netherlands, amassing a 2–0 record with 0.00 ERA, 0.30 WHIP, allowing just two hits, one walk striking out 15 in 10 innings. He was the losing pitcher in the semi-finals against Puerto Rico despite only allowing one run in five innings. He was selected to the all-tournament team.

In the 2014 MLB Japan All-Star Series, Maeda pitched five shut out innings

Maeda also pitched in the 2015 WBSC Premier12 tournament, where he allowed two earned runs while striking out 14 in 12 innings.

On January 7, 2016, Maeda signed an eight-year, $25 million contract with the Los Angeles Dodgers that included $10 million per year in incentives. The deal would have reached a total of around $90.2 million throughout the course of the contract if he reached all of the incentives, which included annual roster bonus of $150,000 if he was on the 25-man opening-day active roster and $6.5 million annually based on starts: $1 million each for 15 and 20, and $1.5 million apiece for 25, 30 and 32 starts. It also had incentives of $3.5 million annually based on innings pitched: $250,000 for 90 and each additional 10 through 190, and $750,000 for 200. The deal was structured in this manner because Maeda’s original physical with the team revealed some unspecified “irregularities.” The Dodgers also paid a $20 million posting fee to the Hiroshima Carp.

Maeda picked up the win in his MLB debut on April 6, 2016, pitching six shutout innings against the San Diego Padres at Petco Park. His first major league strikeout was of Padres starter Andrew Cashner in the top of the second inning. He also hit a home run off of Cashner in his second at-bat for his first major league hit. He made a team high 32 starts with a 16–11 record and 3.48 ERA and was selected by Baseball America to their all-rookie team. He made three starts in the post-season for the Dodgers, losing one game in the Division Series and pitching two no-decisions in the Championship Series. He allowed eight runs in 10⁄3 innings. He finished third in the voting for the National League Rookie of the Year Award behind his teammate Corey Seager and Trea Turner of the Washington Nationals.

In 2017, Maeda began the season in the starting rotation but struggled in April and May, with a 5.16 ERA causing him to be taken out of the rotation and tried in relief. He pitched three innings out of the pen on June 9th to pick up his first career save. On June 18th he was back in the rotation and allowed only one run on three hits in five innings but he returned to the bullpen after that game because the Dodgers had too many starting pitchers on the roster. However, he only appeared in one game in relief before returning to the starting rotation and from June 18th through August 25th, he had went 8–2 with a 2.70 ERA as a starter. At the end of the season, the Dodgers moved Maeda back into the bullpen in order to try him in that role for possible use in the playoffs. Overall during the regular season he appeared in 29 games with 25 starts and had a record of 13–6 with a 4.22 ERA. He did make the post-season roster as a relief pitcher. He pitched two scoreless innings with four strikeouts in the 2017 NLDS and three scoreless innings in the 2017 NLCS. In the 2017 World Series, which the Dodgers lost in seven games, Maeda pitched 5⁄3 innings over four games and allowed one run on four hits. Right-handed batters had just four hits in 32 at-bats against him in the post-season.

And also, On October 29, 2018, he was selected MLB All-Stars at 2018 MLB Japan All-Star Series

On February 10, 2020, the Dodgers traded Maeda, Jaír Camargo and cash considerations to the Minnesota Twins for Brusdar Graterol, Luke Raley and the 67th draft pick in the 2020 MLB draft.

On July 25, 2020, Maeda made his Twins debut. On August 12, he earned the 50th MLB career win.

In the 2020 season, he was 6-1 with a 2.70 ERA. He led the AL in WHIP (0.750). He finished as the runner-up for the 2020 Cy Young Award behind Shane Bieber.