Guzmán was signed as a non-drafted free agent by the San Diego Padres on April 17,. In 2004, he led all minor leaguers in stolen bases, with 90. He made his major league debut on August 17,, going 1–5 with a walk. He got a hit in his first six games in the majors. He missed all of the season following Tommy John surgery. Guzman hit his first MLB home run on September 11,, at Comerica Park off left-handed pitcher Clay Rapada. Guzmán is well known in the minor leagues for his base running. He has had 443 stolen bases over 8 seasons. He was ranked by Baseball America as the second-best prospect in the Padres organization in 2004. In 2007, he came to spring training to compete with Kenny Lofton, Marlon Byrd, and Jerry Hairston, Jr. for playing time in center field, but Guzmán did not make the opening day roster and played the entire season with Triple-A Oklahoma.
On December 5, 2007, Guzmán was traded to the Detroit Tigers for Chris Shelton. Just before the end of spring training, he was sent outright to the minors.
He became a free agent at the end of the season, and signed a minor league contract with the Seattle Mariners. On May 11, 2009, Guzman was released by the Mariners.
On August 31, 2009, the Orioles traded him to the New York Yankees for a player to be named later. On September 14, Guzmán was called up to the Yankees.
In February 2010, Guzmán signed a minor league contract with the Philadelphia Phillies.
Tampa Bay Rays
Guzmán played in the Mexican League during the 2011, 2012, and 2013 seasons. The Tampa Bay Rays signed Guzman to a minor league contract on August 30, 2013. His contract was purchased by the Rays on September 17. He appeared in one game for Tampa Bay, pinch-running for Matt Joyce in the bottom of the 11th down 3-2. Guzmán stole second, then scored the tying run on David DeJesus's RBI single to tie the game, which they won the next inning 4-3. He was outrighted off the roster on October 30, 2013.
On April 15, 2016, Guzman was released by the Vaqueros Laguna of the Mexican Baseball League.
Toros De Tijuana
On April 23, 2016, Guzman signed with the Toros de Tijuana of the Mexican Baseball League. On May 2, 2016, Guzman was released by the Toros de Tijuana.
