Born in Buenos Aires, Zabaleta was raised in Arrecifes. He began his career at Club Atlético San Lorenzo de Almagro in 2002 after progressing through their youth ranks, having been signed at the age of 12 from local club Obras Sanitarias. He started playing as a defensive midfielder but eventually moved to the right side of midfield.

At the age of 14, Zabaleta was called up by Hugo Tocalli to the Argentina under-15 squad. He took part in many youth tournaments, including the FIFA U-20 World Cup in 2003 and 2005, winning the latter in the Netherlands. He received over 75 caps to national youth sides, and started representing the senior side in 2005. He was also a member of the gold medal-winning team at the 2008 Summer Olympics, starting at right-back and playing all six matches.

Zabaleta was transferred to Espanyol in 2005 for €3 million after being Argentina under-20s captain in the 2005 FIFA World Youth Championship, which Argentina won. During the 2005–06 season, Zabaleta helped Espanyol to win the Copa del Rey, playing the full 90 minutes in the 4–1 victory over Real Zaragoza in the final.

In January 2007, Zabaleta suffered a shoulder injury that kept him off the pitch for almost three months, already having established himself as an undisputed first team choice. Later in the season, he featured in the 2006–07 UEFA Cup final, where Espanyol lost on penalties to fellow Spanish side Sevilla.

In the summer of 2008, Zabaleta transferred to Premier League club Manchester City after rejecting an offer from Juventus. He stated upon joining that “The offer is impossible to reject and not just because of the money … Juventus also wanted me but I wanted to come to England, and to Manchester.” Having passed a medical and agreed personal terms, Zabaleta completed a five-year deal with City on 31 August 2008 for an undisclosed fee, believed to be the buy-out clause Zabaleta had attached to his contract of around £6.45 million. Zabaleta joined a day before Manchester City was bought by the Abu Dhabi United Group, led by Sheikh Mansour, which enabled a wealth of investment in the club.

On 13 September 2008, Zabaleta made his debut for Manchester City in a 3–1 defeat to Chelsea at the City of Manchester Stadium. On 5 October, he received his first red card in English football when he was sent off in a 3–2 loss to Liverpool in his fourth Premier League appearance. He scored his first goal for City on 17 January 2009, the only goal of the game in a 1–0 league win over Wigan Athletic.

On 21 November 2010, Zabaleta scored his second Premier League goal in Manchester City’s 4–1 win against Fulham. In the same match, he assisted a Carlos Tevez goal, helping his compatriot to earn his ninth goal for the club during the 2010–11 season.

After the 2010 FIFA World Cup, for which Zabaleta was not selected by head coach Diego Maradona, under the new Argentina manager he has established himself as first-choice right-back. On 1 June 2011, Zabaleta captained Argentina for the first time in a friendly against Nigeria.

On 1 January 2011, Zabaleta played his 100th game for Manchester City in all competitions, coming off the bench against Blackpool in a 1–0 win at Eastlands. Two weeks later, on 15 January, Zabaleta made his second assist of the season in a 4–3 win over Wolverhampton Wanderers. This win meant that City went top of the league above local rivals Manchester United. However, City’s title challenge faded with a loss of form in February and March 2011.

On 1 May 2011, Zabaleta scored his second goal of the season in a Premier League match against West Ham United. This secured a 2–1 win for the Citizens and put them seven points ahead of Liverpool and Tottenham Hotspur in the race for fourth place.

On 14 May 2011, Zabaleta appeared as an 88th-minute substitute for Carlos Tevez in the 2011 FA Cup Final as Manchester City beat Stoke City 1–0.

In the summer of 2011, it was reported that Italian club Roma were keen on signing Zabaleta, but Manchester City insisted the player was not for sale and Zabaleta agreed a three-year contract in July 2011. On 1 October 2011, Zabaleta started and played the full 90 minutes at right-back in a 4–0 win over Blackburn Rovers at Ewood Park in the Premier League, as regular starter Micah Richards was not available. On 23 October, he was an unused substitute in the convincing 1–6 win over rivals Manchester United at Old Trafford, with Richards starting at right-back.

In November 2011, Zabaleta extended his contract with City until the summer of 2015. Zabaleta said, “I’m in a very good team, and I try to do my best for the club, the team and the fans. I didn’t think twice, I gave a quick answer because I was so happy to sign.” In his first three-and-a-half years at the club, Zabaleta emerged as a cult hero amongst the Manchester City fans who admire his never-say-die attitude and commitment to the club.

On 30 April 2012, he started and played the full 90 minutes in the right-back slot in a 1–0 victory over rivals Manchester United thanks to a first-half stoppage time header by Vincent Kompany from a corner at the City of Manchester Stadium. Zabaleta scored the first goal in City’s dramatic 3–2 win over Queens Park Rangers on the final day of the season, a result which secured the first league title for the club since 1968. On 9 December 2012, Zabaleta scored a late equalising goal in a 3–2 defeat to Manchester United.

On 1 January 2013, he scored the opening goal in a 3–0 win at the City of Manchester Stadium over Stoke City, doubling his goal tally from the previous season. On 25 January 2013, Zabaleta scored his third goal of the season and the only goal of the match in a 1–0 win away against Stoke City in the FA Cup, fourth round. His goal took Manchester City through to the fifth round.

Zabaleta was sent off in the 2013 FA Cup Final against Wigan Athletic for a second yellow card after a clear foul on Callum McManaman 84 minutes into the match. Wigan went on to win 1–0 through a Ben Watson goal in stoppage time. He was the third player to be sent off in an FA Cup final and first for the losing side.

On 2 March 2014, Zabaleta played the full 90 minutes as Manchester City beat Sunderland 3–1 in the 2014 League Cup Final to complete a full set of major honours in English football. On 21 April, he scored his first goal of the season in a 3–1 defeat of West Bromwich Albion at the City of Manchester Stadium. On 11 May, Zabaleta was part of the victory against West Ham that won Manchester City the Premier League, his second in three seasons.

On 21 September 2014, Zabaleta was sent off for a second yellow card due to a challenge on Chelsea’s Diego Costa. Both players received a yellow card, Zabaleta for the initial challenge and Costa for his reaction.

In June 2014, Zabaleta was named in Argentina’s squad for the 2014 World Cup. He made his World Cup debut in Argentina’s 2–1 win over Bosnia and Herzegovina at the Estádio do Maracanã, playing the full match in defence.

On 21 August 2015, it was announced that Zabaleta was out for a month with knee injury. On 17 January 2016, Zabaleta reached 200 appearances for Manchester City in the club’s 4–0 victory over Crystal Palace.

At the 2015 Copa América in Chile, Zabaleta sent in the cross from which his Manchester City teammate Sergio Agüero headed the only goal of the game as Argentina defeated holders Uruguay in their second group match.

Zabaleta made 32 appearances in all competitions in the 2016–17 season scoring two goals; against Watford in the Premier League and against Huddersfield Town in the FA Cup. His final appearance for Manchester City came on 16 May 2017, a 3–1 home win against West Bromwich Albion. After the game he was praised by the City manager, Pep Guardiola, as a “legend”. Zabaleta was given a lifetime season ticket for Manchester City and a shirt that read “Zabaleta 333”, to mark the number of City appearances he made.

On 26 May 2017, Zabaleta signed for Premier League club West Ham United on a free transfer, agreeing to a two-year contract. He was given number five as his squad number.

On 22 May 2018, Manuel Pellegrini was confirmed as manager of West Ham United, reuniting him with his former manager at Manchester City.

In June 2018, he worked as a pundit for the BBC’s Match of the Day 2018 World Cup coverage from Russia.

In May 2019, Zabaleta extended his contract with West Ham Until the summer of 2020. On 5 January 2020, Zabaleta scored his only goal for West Ham, in a 2–0 win against Gillingham in the FA Cup third round. On 10 January 2020, in a match against Sheffield United, Zabaleta became the first Argentinean, and only the third South American, to record 300 Premier League appearances. In June 2020, West Ham confirmed his departure from the club at the end of the month. Zabaleta played 80 times for West Ham over three seasons, scoring one goal.

On 16 October 2020, Zabaleta officially announced his retirement from professional football after 18 years.