He spent his first 13 seasons pitching for the Yokohama Taiyo Whales / BayStars in the Japanese Central League, compiling a record of 87–80, usually as a starter.

He spent the next seven seasons in Major League Baseball (MLB) as a closer and relief pitcher, before finishing his career in Japan with the Tohoku Rakuten Golden Eagles.

In his first MLB season of 2006, Saito finished eighth in the National League Cy Young Award voting.

[1] Dodgers broadcaster Vin Scully bestowed the nickname "The Man from Miyagi" upon him, in reference to the prefecture that encompasses Saito's place of birth.

He was found to have a dislocated cartilage in his right elbow in the spring of 1997 and had to undergo surgery, and he spent the rest of the season rehabbing.

He made his first Major League appearance on April 9, 2006, against the Philadelphia Phillies, pitching 2/3 of an inning without giving up any hits or runs.

After stepping into the closer role recently vacated by fan favorite Éric Gagné, he recorded his first Major League save on May 15, 2006, against the Colorado Rockies.

Saito threw a 159 km/h (99 mph) fastball on June 26, 2007, which is claimed to be the all-time record for a Japanese-born Major League pitcher.

[4] On January 10, 2009, Saito signed a one-year $1.5 (+6) million contract with the Boston Red Sox with a team option for 2010.

[8] Saito had another productive year, appearing in 56 games for the second consecutive season and posting a 2.83 ERA with 69 strikeouts in 54 innings.

His career postseason totals include a 1–0 record in 10 games with a 1.69 ERA, nine strikeouts, no walks, and no home runs allowed.

That day against the eventual NPB champion Fukuoka SoftBank Hawks, Saito took the mound in the ninth inning and faced one batter, striking him out swinging.

In November 2015, Saito agreed to a one-year role as a front office intern in the San Diego Padres organization.

Saito also agreed to serve as a pitching coach for a series of 2016 Japan national baseball team games.