Rodriguez pitched for the Angels from 2002 to 2008, and the Mets from 2009 to midway through the 2011 season. He served as the closer for both teams. He then pitched for the Brewers until July 2013, mostly in a setup role, and for the Orioles for the rest of 2013 before returning to the Brewers for 2014 and 2015, this time as the team's closer.

Rodríguez holds the major league record for saves in a single season, with 62, set in 2008 while pitching for the Angels. He is a three-time league leader in saves (2005, 2006, and 2008) and a six-time All-Star. Rodríguez is one of only six Major League pitchers to accumulate a total of 400 or more saves in his baseball career.

Rodríguez signed as an undrafted amateur free agent in 1998. Originally a starting pitcher, Rodríguez moved to relief pitching in 2002 after elbow and shoulder injuries shortened his 2001 minor league season with the Lake Elsinore Storm. In 2002, he made his major league debut. At the time, he was the youngest pitcher in the American League. Because of the multiple injuries to the Angels bullpen, the club brought him up during the middle of September. He emerged as a postseason relief hero, winning five postseason games despite never having won a Major League game before. Although he threw a lively fastball, his sharp-breaking curveball was his most effective pitch.

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