Fuentes was drafted by the Seattle Mariners (American League) in the 25th round of the 1995 amateur draft. He spent one season for the Mariners appearing in ten games.

On December 16, 2001, Fuentes was traded to the Colorado Rockies (National League), along with José Paniagua and Denny Stark for Jeff Cirillo. Through the first four years of his Major League career, Fuentes had a record of 8-8 with a 4.04 ERA, recording only four saves in 163 games. However, in 2005, Fuentes took over the closer role for the Rockies following the season-ending shoulder surgery of right-handed pitcher Chin-hui Tsao. Fuentes had a successful season and was named to his first career All-Star Game, but did not appear in the game. He became the first reliever and only the third pitcher overall to represent the Rockies, joining starting pitchers Mike Hampton (2001) and Shawn Chacón (2003). His 31 saves matched Dave Veres (1995) for the third highest single season total in franchise history, trailing only José Jiménez (41 in 2002) and Chacon (35 in 2004). In 2006, Fuentes earned 30 saves while posting a 3-4 record and a 3.44 ERA and was selected as an All-Star for the second time. Fuentes got his first career postseason win in Game 3 of the 2007 NLDS when the Rockies won the series against the Phillies in 3 games. The Rockies would eventually make it to the World Series for the first time in franchise history but lost to the Boston Red Sox in the 2007 World Series in just 4 games.

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