Reyna's father Miguel moved to the United States in 1968 from Argentina, where he had gone through the youth system of Independiente and played professionally with Los Andes. He settled in New Jersey where he married a Portuguese American woman, Maria Silva, and raised a family. Reyna learned the game from his father. Born in Livingston, New Jersey, Reyna would go on to become a youth player at Saint Benedict's Preparatory School in New Jersey as a teammate of Gregg Berhalter. He graduated from St. Benedict's in 1991. During Reyna's three years with the team, St Benedict's went undefeated (65–0) while Reyna was named as the only two-time Parade Magazine's national high school Player of the Year and the Gatorade National Player of the Year. In 1999, he was named by The Star-Ledger as one of the top ten New Jersey high school soccer players of the 1990s.
On August 8, 1994, Reyna signed with German Bundesliga club Bayer 04 Leverkusen after playing in the 1994 FIFA World Cup. He had difficulty finding playing time with the Leverkusen first team, making only five appearances. Leverkusen loaned Reyna to fellow Bundesliga side VfL Wolfsburg in July 1997. He quickly established himself in Wolfsburg's first team where he became the first American to captain a European club.
On April 1, 1999, Rangers paid $826,400 to Wolfsburg and $2.76 million to Leverkusen for Reyna. Reyna would remain with Rangers until December 2001. Despite building his reputation in Germany and on the national team as a creative midfielder, he spent most of his years at Rangers playing either defensive midfield or right back. He scored ten goals for the Ibrox club, one of the most notable was a strike that proved decisive over Italian club Parma for qualification for the 1999–2000 UEFA Champions League.
Reyna's time at City was frequently punctuated by injury, restricting him to thirty appearances in his first season with the club, and causing him to miss six months of the 2004–05 season. In three and a half seasons at the City of Manchester Stadium, Reyna made 87 appearances, scoring four goals and was a popular player with City supporters.
On January 11, 2007, Manchester City manager Stuart Pearce announced that the club had agreed to terminate Reyna's contract with a view to a move to Major League Soccer for family reasons. This was finalized on January 23, 2007.
On January 24, 2007, Reyna signed with New York Red Bulls, where he rejoined his former University of Virginia and U.S. national team head coach Bruce Arena. However, much like his years in Britain, Reyna was almost constantly bothered by injuries. He only played in twenty-seven games during two years with New York and only six games in 2008 as he rehabilitated a herniated disc. Reyna announced his professional retirement on July 16, 2008.
In 2002, despite sitting out the opening 3–2 upset win over Portugal due to injury, he was a key contributor in the next three U.S. games — a tie against South Korea, a loss to Poland, and a win over CONCACAF rival Mexico. In the quarterfinals, the U.S. lost to eventual runner-up Germany. He became only the third American ever (after Bert Patenaude and John Souza) named to the World Cup all-tournament team.
In 2006, Reyna again captained the U.S. at the World Cup in Germany. Trailing 1–0 in the opener against the Czech Republic, Reyna fired a 30-yard shot that bounced off the post, the best American chance in the game. In the final group game against Ghana, Reyna suffered a sprained medial collateral ligament when he lost the ball to Haminu Draman who then dribbled in alone and scored Ghana's first goal.
On June 23, 2006, the day after the U.S. was eliminated from the World Cup, Reyna announced his retirement from the national team. He ended his international career with 111 caps and eight goals.
Reyna now spends much of his time managing the Claudio Reyna Foundation, his non-profit established to provide soccer training and mentoring to underprivileged youth around the nation and abroad. Claudio was elected to the National Soccer Hall of Fame on February 29, 2012.
On July 19, 2012, Reyna's 13-year-old son Jack lost his fight with cancer.
^Trecker, Jerry (January 16, 1994). "WORLD CUP '94 Making A Quick Point Newcomers, one local, help USA over Norway". Newsday. Retrieved April 28, 2013. "Chasing down a long throw from former Blau-Weiss Gottschee star Dario Brose, [Claudio Reyna], the 1993 College Player of the Year from the University of Virginia and Livingston, N.J., slammed a hard shot at Norway goalkeeper Frode Grodas to create a game-winning rebound chance for Cobi Jones as the United States defeated Norway, 2–1, in Sun Devil Stadium yesterday to begin its 1994 World Cup preparation with an upset triumph."