He was named in the Team of the Tournament for the 2002 FIFA World Cup, and elected to the National Soccer Hall of Fame in 2012.

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.

On an individual level, Reyna won the Hermann Trophy in 1993[8] and the MAC Award in 1992 and 1993;[9] and was named the 1992 and 1993 Soccer America Player of the Year.

[11] On August 8, 1994, Reyna signed with German Bundesliga club Bayer 04 Leverkusen after playing in the 1994 FIFA World Cup.

He completed the deal minutes before the midday deadline, having played for Rangers in the UEFA Cup at Paris Saint-Germain the night before.

[14] Reyna made his debut on December 15, starting in a 2–0 loss at Southampton in place of the injured Julio Arca, and had a 20-yard first-half shot saved by Paul Jones.

[18] In October 2002, Reyna injured the anterior cruciate ligament in his knee against Bolton Wanderers, ruling him out for six months and ending his season.

[21] 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.

[22][23] 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.

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.

Reyna led the club in its 2021 inaugural season with his former US national team teammate, Austin FC head coach Josh Wolff.

On January 26, 2023, Reyna resigned from his role as sporting director amid a personal scandal, remaining as a technical advisor for the club.

[42] During and after the 2022 World Cup, Claudio and Danielle Reyna were reported to have intervened with the United States Soccer Federation, making "veiled threats" in an attempt to get Giovanni additional playing time and better treatment with the United States national team, and even attempting to blackmail then-coach Gregg Berhalter.

A report by the USSF found that facts gathered during the investigation "might raise a question about whether Mr Reyna's communications with US Soccer officials are violative of the FIFA Code of Ethics and its rule against abuse of position".

[44] As a result of the scandal, Reyna stepped down from his position at Austin FC, and the USSF re-wrote its guidelines to limit parent/coach interactions.