Lopez was first signed by the Seattle Mariners on July 3, 1997, and made his Major League debut on April 2, 2003, after being selected by the Toronto Blue Jays on December 16, 2002, as a Rule 5 draftee.

He made 72 appearances in 2003 for the Blue Jays, recording 14 saves and posting a 3.42 ERA over 73+2⁄3 innings.

He was a member of the Colorado Rockies, Los Angeles Dodgers, Philadelphia Phillies and San Diego Padres organizations from 2005 to 2006, mostly as a Minor League player.

In 2008, after spending most of the season with the Tigers, Lopez was sent down to Toledo when Fernando Rodney was activated from the disabled list.

[1] Although his ERA on the season was a comparatively low 3.55, he allowed 50.9% of inherited runners to score, the second-highest in the American League.