Cruz was born in Arroyo, Puerto Rico. His father José Cruz was a baseball player and coach, and the family lived in Texas. He attended high school in Bellaire, Texas, when his father was a member of the Houston Astros. After graduation from Bellaire, Cruz enrolled at Rice University and played baseball for the Owls, starting for four seasons.
The Seattle Mariners selected Cruz in the first round of the 1995 Major League Baseball draft. He played 12 years as an outfielder in the MLB, with Seattle in 1997, the Toronto Blue Jays from 1997 to 2002, the San Francisco Giants in 2003, the Tampa Bay Devil Rays in 2004, the Arizona Diamondbacks in 2005, the Boston Red Sox in 2005, the Los Angeles Dodgers from 2005 to 2006, the San Diego Padres in 2007 and the Houston Astros in 2008.
In 2021, Cruz was named the assistant hitting coach of the Detroit Tigers, but he left the position on June 12 to accept the head coaching job at Rice University. He is the son of former major league outfielder and Houston Astros first base coach José Cruz, and the nephew of former big leaguers Héctor and Tommy Cruz.

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