Pierre was drafted twice while in college, in 1995 and 1996 by the Seattle Mariners, but did not sign either time. Pierre played at the University of South Alabama where he was selected as the Sunbelt Conference Player of the Year in 1998. That same year he was drafted by the Colorado Rockies on June 2, 1998.

After spending a few seasons with the Rockies' minor league affiliates, Pierre was called up to make his MLB debut on August 7, 2000. He played 51 games that year, hitting 26 runs and finishing with a .310 batting average. He was also fifth in voting for the MLB Rookie of the Year award.

He spent the next two seasons as a full roster member with the Rockies. On November 16, 2002, Pierre was traded to the Florida Marlins.

Pierre made his first post season appearance with the Marlins in 2003, winning the World Series with the team over the New York Yankees.

He continued with the Marlins through the 2005 season, after which he was traded to the Chicago Cubs on December 7. He stayed with the Cubs for only a single season, entering free agency at the end of the year.

On November 22, 2006, Pierre signed with the Los Angeles Dodgers, playing a full season, 162 games in 2007, and on the starting roster in 2008.