A right-hander, he pitched all or parts of 14 seasons in Major League Baseball, primarily as a relief pitcher.

During his major league career, Worrell pitched for nine teams, including the San Diego Padres, Cleveland Indians, Detroit Tigers, Oakland Athletics, Baltimore Orioles, Chicago Cubs, San Francisco Giants (twice), Philadelphia Phillies, and Arizona Diamondbacks.

On May 6, 2005, Worrell stated that he was dealing with "personal psychological issues" that had to be resolved and was subsequently placed on the 15-day disabled list.

Seemingly back to his old self, Worrell returned to pitch a perfect ninth on July 4, 2005, and completed the season in Arizona with an exceptional 0.90 ERA over his last 18 games.

On December 1, 2005, Worrell's return to the San Francisco Giants was confirmed, with a two-year contract valued at $4 million.