Matthews was drafted by the San Diego Padres on June 3, 1993. He joined the Padres' minor league affiliates in 1994 for his first few years. On June 4, 1999, Matthews was called up to make his MLB debut with the Padres, playing 23 games that season.

On March 23, 2000, Matthews was traded to the Chicago Cubs, where he played through August of 2001, when he was waived. Matthews was claimed by the Pittsburgh Pirates on August 10, where he finished the 2001 regular season. On December 28, 2001, his contract was purchased by the New York Mets. Matthews played only two games with the Mets in 2002 before he was traded to the Baltimore Orioles on April 3, 2002.

After just over a full year with the Orioles, Matthews was claimed off of waivers by the San Diego Padres on May 23, 2003. He finished the 2003 season with the Padres and was again waived following the season. He was then claimed by the Atlanta Braves, but was released on April 2, 2004, not playing a single game in a Braves uniform.

Matthews signed as a free agent with the Texas Rangers on April 8, 2004. He stayed with the Rangers for the next three seasons, including in 2006, when he was selected for his first MLB All-Star Game.

Following the 2006 season, Matthews signed as a free agent with the Los Angeles Angels of Anaheim on November 22, 2006. In December of 2007, Matthews was named in the Baseball Mitchell Report for alleged steroid use.