[5][6] He won six European league titles across La Liga and Serie A. Higuaín started his career with Argentine club River Plate, before a transfer to Real Madrid in January 2007.

[15] Higuaín started playing in the youth teams and made his debut with River Plate in a 2–1 defeat against Gimnasia y Esgrima (LP) on 29 May 2005.

[18] Following his brace in the Superclásico derby against Boca Juniors on 8 October 2006, River Plate manager Daniel Passarella declared that Higuaín had an "enormous future" and was "destined for superstardom".

Because of this, he started to gain international recognition and became one of the leading goalscorers of La Liga, alongside his Barcelona counterpart Samuel Eto'o.

[26] On 21 April 2009, Higuaín played very well in the match against Getafe and scored the decisive goal in the last minute, giving Real Madrid a 3–2 victory which enabled the team to keep close to Pep Guardiola's Barcelona in the league table.

He ended the season with 22 league goals[28] and 24 in all competitions, around as many as established football stars including Diego Forlán, David Villa and Thierry Henry.

[39][40] On 29 August 2012, Higuaín scored the opener in an eventual 2–1 win against Barcelona in the second leg of the 2012 Supercopa de España, which secured Real Madrid its first title of the season.

[42] He scored again in the next match, a 2–1 loss to Getafe CF at Coliseum Alfonso Pérez, which marked Real Madrid worst league start in 39 years.

[52] On 18 September, Higuaín scored in Napoli's opening Champions League fixture, a 2–1 victory over Borussia Dortmund at the Stadio San Paolo.

[55] On 12 February 2014, Higuaín scored two goals in Napoli's 3–0 defeat of Roma in the semi-final of the Coppa Italia, taking the team to the final with a 5–3 aggregate victory.

[60] In the 2014 Supercoppa Italiana against Juventus in Doha, Qatar, on 22 December, Higuaín equalised twice, forcing extra time and then a penalty shootout, in which he was one of the scorers in a Napoli victory.

[61] Higuaín scored a hat-trick, including a penalty, on 12 March 2015, as Napoli came from behind to defeat Dynamo Moscow 3–1 in the first leg of the last 16 of the UEFA Europa League.

[65][66] Higuaín scored twice in Napoli's 3–1 win over Sassuolo on 16 January 2016 to extend the team's lead to four points; his second goal of the game was his 20th of the campaign.

[81] On 5 April 2017, Higuaín scored twice against Napoli in the 2016–17 Coppa Italia second semi-final leg to put Juventus through to the final 5–4 on aggregate, in spite of a 3–2 away loss.

[96] On 1 July 2019, Higuaín returned to Juventus as Chelsea declined to extend his loan; thus, he was once again reunited with manager Maurizio Sarri, who had recently joined the club.

[103] On 31 July 2022, Higuaín scored another free-kick for Inter Miami, and then netted two more goals to complete a first-half hat-trick in 27 minutes against FC Cincinnati in a 4–4 draw.

[105] Higuaín is one of only three foreign-born players to have played for Argentina in a FIFA World Cup, along with Pedro Arico Suárez[106] and Constantino Urbieta Sosa.

Higuaín was selected for Argentina by coach Diego Maradona for the last 2010 FIFA World Cup qualification games against Peru and Uruguay.

[114] Higuaín was a member of Sergio Batista's Argentine squad for the 2011 Copa América on home soil, making one substitute appearance and one start in the group as Carlos Tevez was preferred at centre forward; Argentina advanced in second place behind Colombia.

He started against Uruguay in the quarter-finals in Santa Fe, and equalised in the 17th minute by heading Lionel Messi's cross past goalkeeper Fernando Muslera; he later had another goal disallowed for offside.

[119] On 22 March 2013, Higuaín scored twice as Argentina beat Venezuela 3–0[120] to make him top scorer in the South American section of World Cup qualifying with nine goals.

[122] After appearing as a half-time substitute in Argentina's 2–1 defeat of Bosnia and Herzegovina at the Maracanã Stadium on 15 June, Higuaín exchanged passes with Messi to assist his captain for the winning goal.

[127] With Sergio Agüero preferred as the lone centre-forward in a three-man Argentine attack, Higuaín made his first start of the 2015 Copa América in the final group match, against Jamaica in Viña del Mar.

Winning his 50th cap, he scored the only goal of the game in the 11th minute when set up by Ángel Di María, sending Argentina through to the quarter-finals as group winners.

[130][131][132] At the Copa América Centenario in 2016, Higuaín was named to Gerardo Martino's 23-man Argentina squad, and was selected as his team's starting centre forward.

[130][136][137] During Argentina's troublesome qualifying campaign for the 2018 FIFA World Cup in Russia, Higuaín managed only one goal in nine appearances, and eventually lost his place in the team's starting line-up.

[140][141][142][143] On 28 March 2019, in an interview with Fox Sports Argentina, Higuaín announced his retirement from international football, where he defended himself, commenting: "My era with the Selecc[í]on is over, now I will be watching the team from the outside, which I'm sure will make many people happy.

[143][144][145] Nicknamed El Pipita or Pipa,[146] as was his father Jorge, who was also a footballer, Higuaín was a hardworking right-footed striker and a prolific goalscorer.

He was known in particular for his great striking ability with either foot in the last 25 yards,[147][148] as well as his opportunism and clinical finishing inside the penalty area, while his height, eye for goal, and strong physique made him a dangerous aerial presence in the box.

A well-rounded striker, he also possessed good technical skills, and an ability to drop deep, link-up with teammates, hold up the ball, and lay it off to other players.