Hisashi Iwakuma participant of 2012 Major League Baseball season
Seattle Mariners
Iwakuma signed with the Seattle Mariners prior to the 2012 Major League Baseball season, for $1.5 million guaranteed, plus an additional $3.4 million in incentives linked to starts, innings pitched, and awards. He was part of the Mariners' bullpen to start the season and did not pitch until the club's fifteenth game, making him the last member of any team's opening day roster (who was not injured or demoted to the minor leagues) to appear in a game. Iwakuma later became an effective member of the Mariners' pitching staff, pitching in 30 games (16 starts and 14 relief appearances), going 9–5 with two saves and a 3.16 earned run average.
On November 2, 2012, Iwakuma agreed to a two-year, $14 million extension with an option for 2015. Iwakuma earned $6.5 million in 2013 and 2014, and his option for 2015 is worth $7 million with a $1 million buyout. Iwakuma was chosen along with fellow pitcher Félix Hernández to represent the Mariners at the 2013 MLB All-Star Game. However, he did not pitch, as he had played on the Sunday before the game. On September 18, 2013, Iwakuma pitched eight scoreless innings against the Detroit Tigers striking out Miguel Cabrera twice making him 0 for 4 and lowering his batting average to .347. He gave up no runs and four hits getting out of two bases loaded jams in the first and fourth.
Iwakuma finished third in the 2013 American League Cy Young Award voting, behind winner Max Scherzer and runner up Yu Darvish. He finished the year third in the league in ERA, third in innings pitched, second in WHIP and first in WAR. His 2013 season year finished 14–6 with a 2.66 ERA and a 1.00 WHIP.
Iwakuma sustained a strained tendon in his finger in February 2014 and was expected to miss 4–6 weeks. On May 3, Iwakuma returned from the DL to play against the Houston Astros. Making 28 starts in 2014, Iwakuma finished 15–9 with a 3.52 ERA.
On April 21, 2015, Iwakuma was placed on the DL with a strained lat muscle. He was activated by Seattle on July 6.On August 12, 2015, at Safeco Field against the Baltimore Orioles,  Iwakuma threw the fifth no-hitter in Mariners history. It was also his first MLB complete game. For his effort, Iwakuma won the American League Player of the Week Award. Making 20 starts in 2015, Iwakuma finished with a 9–5 record and a 3.54 ERA.On December 17, 2015, Iwakuma re-signed with the Mariners on a 1-year contract, with vesting options for 2017 and 2018. Iwakuma had previously attempted to sign a three-year, $45 million deal with the Los Angeles Dodgers, but the deal was declined because the Dodgers had some concerns about the results of his physical.On May 10, 2017, Iwakuma was placed on the 10-day disabled list due to right shoulder inflammation. He was later moved to the 60-day disabled list. On November 2, 2017, the Seattle Mariners declined their option making him a free agent. He signed a minor league contract with an invitation to spring training with the Mariners on November 27. On September 11, 2018, he announced that he would return to Japan to play baseball after spending the entire season in the minors.