He played in Major League Baseball for the Chicago Cubs, Atlanta Braves, Oakland Athletics, Arizona Diamondbacks, Kansas City Royals, Tampa Bay Rays, and Pittsburgh Pirates from 2001 to 2012.

On March 25, 2004, Cruz, along with Steve Smyth, were acquired by the Atlanta Braves, from the Chicago Cubs, for Andy Pratt and Richard Lewis.

[1] In 2004, with the Braves, Cruz went 6–2 with a 2.75 ERA in 50 relief appearances while setting a career high in wins and games pitched, and placed second in the Atlanta bullpen with 8.75 K's per 9 innings.

On December 16, 2004, the Oakland Athletics acquired Cruz, along with Dan Meyer and Charles Thomas, from the Atlanta Braves, in exchange for Tim Hudson.

Cruz returned to the big-league team in September 2005 when rosters expanded, and he recorded a 4.82 ERA in his last 7 games of the season.

After going 2–0 with 10.1 scoreless innings for Oakland in 2006 Spring Training, Cruz was dealt to the Arizona Diamondbacks for pitcher Brad Halsey.

Cruz began the year in the starting rotation, and went 3–3 with a 4.05 ERA and 41 K's in 14 games, before being placed on the day-to-day disabled list with shoulder soreness on June 6.

On February 28, 2009, the Kansas City Royals signed Cruz to a two-year, $5.5 million contract with a club option for the 2011 season.

But on February 13, 2013, before the first Spring Training workout began, the Phillies released Cruz after they mutually agreed to rescind their agreement.