He has also played in Major League Baseball (MLB) for the Los Angeles Dodgers and Toronto Blue Jays.

Ryu started the semifinal match against Chinese Taipei (Taiwan), and helped his team reach the final, recording ten strikeouts and giving up one unearned run on four hits in six innings.

In July 2005, Ryu was selected by the Hanwha Eagles as the 1st pick in the second round of the 2006 KBO League Draft, and made his professional debut on April 12, 2006.

[8] In 2006, he became the first Korean pitcher to participate in the Doha Asian Games since Lotte Giants Joo Hyung-kwang in 1996, with 18 wins, 6 losses, 204 strikeouts and a 2.23 ERA.

In the team's third game of round-robin play, Ryu pitched a 1–0 complete-game shutout victory over Canada, giving up five hits.

On May 11, 2010, Ryu became the first pitcher in history to strike out 17 batters in a nine-inning game, against the LG Twins at Cheongju Sports Complex Baseball Stadium.

Finally, on October 29, 2012, the Eagles announced that Ryu would be posted as early as November 1, 2012 to allow MLB teams to bid for the rights to negotiate with him.

On November 9, 2012, the Eagles accepted the reported bid of $25.7M from the Los Angeles Dodgers, giving them a 30-day period to try to negotiate a contract with Ryu.

[10] On March 17, 2013, Ryu recorded his first win as a Dodger, albeit, in a spring training game on St. Patrick's Day.

[15] On May 1, 2013, Ryu pitched six innings against the Colorado Rockies and struck out 12 batters, his highest strikeout count in an MLB game so far.

[18] On October 6, 2013, Ryu became the first South Korean to serve as the starting pitcher of a Major League Baseball postseason game.

[23][24] The Dodgers noted a lack of velocity in his bullpen session soon afterwards,[25] and Ryu decided to have a surgery on his shoulder to alleviate the problem.

[36] Ryu became a free agent after the season, but accepted the Dodgers one-year, $17.9 million, qualifying offer to remain with the club for 2019.

[37] Ryu was named the Dodgers opening day starter for the 2019 season after injuries to Clayton Kershaw and Rich Hill.

In his next start against the Washington Nationals on May 12, 2019, he had a no-hit bid before giving a double to Gerardo Parra in the eighth inning with one out.

This streak is tied for the tenth longest in Dodgers' history and is 28 fewer than the team record of 59 set by Orel Hershiser in 1988.

[43] He finished the regular season with a record of 14–5, an MLB season-leading ERA of 2.32 and the lowest walks per nine innings ratio of 1.183.

On September 24, 2020, in his final regular season start, Ryu became the first Blue Jays' starting pitcher in that season to pitch into the 7th inning & the second starter to throw 100 pitches, while also yielding 0 runs, 5 hits, & 2 walks, while compiling 4 strikeouts and the winning decision in a 4–1 victory over the New York Yankees to help clinch the Blue Jays' first postseason berth since 2016.

[49] Hyun-jin made 31 starts for Toronto in 2021, pitching to a 14–10 record and 4.37 ERA with 143 strikeouts and 37 walks in 169.0 innings of work.

On June 2, 2022, he was pulled from a start against the Chicago White Sox shortly after reaching 1,000 career innings pitched.

[50] On August 1, 2023, Ryu made his season debut and his first start in a year with the Blue Jays in a 3–13 losing effort against the Baltimore Orioles.

On February 20, 2024, Ryu reached an agreement to return to South Korea to play for his old team, the Hanwha Eagles, for eight years and 17 billion won, the largest contract in KBO League history.

[59] Through the 2019 season, Ryu is the only pitcher born in Asia with a sub 3.00 career ERA (minimum of 500 innings pitched) in major league history.