IHeinze began his career in his home country with Newell's Old Boys in Rosario. Following attention from various European clubs, he then signed for Real Valladolid. After just one season with the Spanish club, he was loaned to Sporting in Portugal, though he would return and spend a further two years in Spain.

At the close of the 2001 season, he moved to Paris Saint-Germain and here he enjoyed over 119 appearances and 19 goals in the three years he stayed, winning the French Cup in 2004.

He marked his debut for United in September 2004 with a goal in the 2-2 draw against Bolton Wanderers and immediately established himself as United's first choice left-back. The Manchester United fans took to the Argentine for his exemplary attitude, showing fierce determination on the pitch.[citation needed] Heinze's impressive play was regularly lauded by United fans with the familiar chant of "Ar-gen-tina!" Heinze was voted Manchester United fans' player of the year for the 2004-05 season (unusually rare for a player to be voted in the first season in the club, even more so as a defender), beating top-scorer Wayne Rooney, and is the first South American to do so.

Heinze was injured in a UEFA Champions League match with Villarreal on 13 September and was out of first-team action for the rest of the 2005-06 season. United suffered a dip in form in Heinze's absence, further highlighting the Argentine's importance to the Manchester club. Kieran Richardson, John O'Shea and new arrival Patrice Evra all tried and ultimately failed to impose themselves in Heinze's left-back position, and while Mikaël Silvestre brought some stability to the position towards the end of the season, Ferguson said that his team missed Heinze's experience and leadership.[citation needed] Gabriel made a comeback of sorts for the reserve team in April, but a minor injury picked up in his third game back prevented him making a first-team appearance before the end of the campaign, and this appeared to have ended his chances of representing Argentina in the 2006 World Cup in Germany. However, national coach José Pekerman showed great faith in Heinze and called him up into his 23-man squad for the finals.

Heinze returned to action for United in the 2006-07 season. He scored his first goal of the season in the FA Cup 5th round replay against Reading, in a 3-2 win to United on 27 February 2007. Due to United's injury problems, with the likes of Rio Ferdinand, Nemanja Vidić and Gary Neville being unavailable, Heinze was used as a centre-back partnering Wes Brown where he has struggled to live up to the standard required for the position.[citation needed] Heinze was made captain of United for their last two games of the 2006-07 season, away to Chelsea, and at home to West Ham.

On 21 July 2007, a bid in the region of £6.8 million from Liverpool was rejected by United, amid complaints by Sir Alex Ferguson as to the conduct of the player's agent and unwillingness to sell to a club perceived as a rival.[5] Heinze appealed to the Premier League for arbitration but his case was dismissed on 21 August 2007 by the tribunal, which ruled that Manchester United were not obliged to sell the player to Liverpool.

On 22 August 2007, Heinze joined Real Madrid on a four year deal, for a reported £8 million.