On 31 July 2010, Márquez was released from his contract by Barcelona. During his time with the club, he played in 242 matches and scored 13 goals, making him the most-capped non-European player in the club's history and the eighth-most capped foreigner. In his 12-year European career, Márquez appeared in 46 UEFA Champions League matches, which was the most by a Mexican or CONCACAF player, until compatriot Javier Hernández surpassed that record in 2017. At the time, Márquez was also one of two players from CONCACAF to play in a Champions League final, the other being Trinidad and Tobago's Dwight Yorke.
On 1 August 2010, it was announced that Márquez had signed with the New York Red Bulls of Major League Soccer on a three-and-a-half-year contract. He was the club's third Designated Player and was unveiled to the media at Red Bull Arena on 3 August wearing the number 4 jersey and reuniting with former Barcelona teammate Thierry Henry. On 8 August, Márquez made his MLS debut against the Chicago Fire in a scoreless draw. On 21 August, Márquez scored his first goal, an astonishing shot with his right foot, for the Red Bulls in a 4–1 win at Toronto FC. On 21 October, Márquez started for the Red Bulls in a 2–0 victory over New England Revolution which clinched the regular season Eastern Conference title.