He played in Major League Baseball (MLB) for the Toronto Blue Jays, Seattle Mariners, and Los Angeles Dodgers.

[1] He made his major league debut on September 21, 2004 against the New York Yankees as he pitched a solid inning and a third.

[2] Following League's breakout season in 2006, he engaged in strength conditioning during the offseason, and at the behest of the Blue Jays, did not pitch until spring training.

On December 22, 2009, League was traded to the Seattle Mariners along with minor-league outfielder Johermyn Chávez for pitcher Brandon Morrow.

In a 2011 interview, veteran outfielder Coco Crisp named League as one of the four toughest pitchers he had ever faced.

[7] On June 8, 2012, League was one of six Mariners to throw a combined no-hitter against the Los Angeles Dodgers at Safeco Field.

On July 30, 2012, League was traded to the Los Angeles Dodgers for minor leaguers Leon Landry and Logan Bawcom.

[10] On June 11, League was demoted from the closer role after blowing his fourth save in 17 chances, and he was replaced by Jansen.

[1] League underwent an MRI during spring training in 2015 which revealed serious shoulder damage, causing him to miss the first couple months of the season.

On January 30, 2025, the Cleveland Guardians hired League to serve as the pitching coach for their Triple-A affiliate, the Columbus Clippers.