In 2007, he was disputed over by Barcelona and Real Madrid, after offers from Valencia, Sevilla, Espanyol, Deportivo La Coruña, Arsenal and Liverpool. Barcelona won the race for Icardi, and signed with him until 2013.

Icardi joined the Catalan club at the start of 2008–09 season and was included on the U-17 team. He was promoted to the U-19 team the following season before joining Sampdoria on loan in January 2011. Icardi later stated that leaving Barcelona was not a bad decision, convinced that his decision to move on was the right one.

On 11 January 2011, Sampdoria confirmed Icardi had signed with the club on loan until the end of the season. After a successful six-month loan for la Samp, scoring 13 goals in 19 games with the Primavera team, the Italian side utilised the option to buy Icardi for €400,000 in July 2011, signing a three-year deal. In 2011–12 season, he scored 19 goals in the reserve league Group A, as the joint-third topscorer of the league along with Gonzalo Barreto of Group C.

On 12 May 2012, he made his first-team debut, against Juve Stabia, after coming off the bench to replace Bruno Fornaroli in the 75th minute of the match. Ten minutes later, Icardi scored his first professional goal to win the match 2–1 for Sampdoria.

On 26 September 2012, he made his Serie A debut for Sampdoria against Roma, substituting the Paraguayan midfielder Marcelo Estigarribia in the 49th minute. On 12 November, Icardi scored his first goal in Serie A in the Derby della Lanterna against Genoa in an eventual 3–1 win. On 6 January 2013, he scored two goals against Juventus in Sampdoria’s 2–1 upset at Juventus Stadium. It was Juventus’s second ever loss in the Juventus Stadium since the construction.

Later on 15 October, Icardi scored all three goals as Inter defeated cross-town rivals Milan 3–2 to put Inter in second place. He became the first player to score a hat-trick in the Derby della Madonnina since Diego Milito in May 2012. Later on throughout the season, on 18 March 2018, Icardi scored four goals, including a 14-minute hat-trick, his 6th in Serie A, against his former club, Sampdoria, to give Inter a 5–0 win at the Stadio Luigi Ferraris. Furthermore, he broke the 100 goal mark in Serie A during the same match, taking his total tally to 103 Serie A goals in his 180th Serie A appearance, becoming the 6th youngest player ever to achieve this feat, at the age of 25 years and 27 days; his fourth goal of the match was also his 100th goal for Inter, in his 172nd appearance for the club.

In April 2012, Icardi received a call-up from Italy under-19 squad to play in the friendly against England, but the player refused to accept the invitation as he wanted to play for Argentina. His wish was fulfilled on 26 July where he was summoned by Argentina under-20 coach Marcelo Trobbiani to play in the friendly against Germany, in which he made his debut on 14 August at Commerzbank-Arena, and the L’Alcúdia Tournament, held in Valencia, Spain.

On 27 January 2013, he scored four goals in a six-goal thrashing of fellow strugglers Pescara, lifting the Genoese side clear of the Serie A relegation zone. On 18 May, during the final match of 2012–13 season, Icardi scored again against Juventus, helping the team to beat the eventual champions of Italy 3–2 at Stadio Luigi Ferraris.

On 25 August 2013, Icardi made his Inter official debut, coming on as a second-half substitute in a 2–0 home success over Genoa, hitting the crossbar late in the game; he scored his first league goal for the Nerazzurri on 14 September, netting the first of a 1–1 home draw against Juventus, after coming on as a substitute in the 73rd minute.

Following Italy national football team manager Cesare Prandelli’s interest in Icardi’s performances, in February 2013, Icardi stated his wish to play for the Argentina senior team, despite also being eligible to play for Italy, saying: “I’m very grateful to Italian football for the opportunity it has given me, I’d also like to thank Prandelli for the nice words he expressed about me. But I have to be honest and sincere – I’m Argentine, I feel Argentine, and I’ve always dreamed of wearing the shirt of my nation. To actually do that would be the maximum for me.”

On 15 October 2013, he played his first game for the main squad, coming on as an 82nd-minute substitute for Augusto Fernández in a 2–3 FIFA World Cup qualifier loss away to Uruguay.

Nicknamed El niño del partido, Icardi is a quick, tactically intelligent, and physically strong striker, with good technique. Known for his excellent attacking movement, positioning, an eye for goal, he mainly operates in central areas inside the penalty box; an accurate and efficient finisher with his head and either foot inside the area, he is known for his ability to score from few touches, although he can also hold up the ball in order to create space or chances for other players, and play off of his teammates. Although he was once criticised for his limited creative and defensive contribution, as well as his lack of significant pace, stamina, power, and movement outside the box, his work-rate has improved in recent seasons, and has seen him drift out to wide positions in order to create space or provide assists for teammates. Long regarded as a talented and promising prospect, in 2013, Don Balón listed him as one of the top 100 young players born after 1992.

Icardi is married to Argentine media personality Wanda Nara. Nara was married to Icardi’s former Sampdoria teammate Maxi López, but the couple split after her relationship with Icardi was exposed. She and López began divorce proceedings in December 2013. Nara and Icardi subsequently married on 27 May 2014, not long after the divorce was finalised, at a small ceremony in Buenos Aires. They have two daughters, Francesca, born on 19 January 2015, and Isabella, born on 27 October 2016.

Due to injury, Icardi missed most of the games of the first part of the season, only returning to first-team matches in February. On 14 February 2014, during the away match against Fiorentina at Stadio Artemio Franchi, Icardi returned in the field after four months and scored the winner after only ten minutes. Later, on 5 April, Icardi scored a brace during the 2–2 home draw against Bologna. That was his first brace of his Inter career. This was followed by another brace during the 0–4 away win against his former side Sampdoria. Before the match, he was booed by the home fans, but he quieted them down by scoring in the 13th minute from a cross from Palacio, making a negative gesture which saw him booked.

On 10 May 2014, in Javier Zanetti’s last competitive match at the San Siro, in which Inter defeated Lazio 4–1 to secure a place in Europa League play-off for next season, Icardi scored the second goal of the match in the 37th minute after an assist from Kovačić and went to celebrate with Zanetti. He ended his first season with Nerazzurri with 23 matches in all competitions, including 22 in the league, scoring 9 goals in the process with an average of one goal in every 145 minutes.

On 10 June 2014, Inter and Sampdoria reached the deal to terminate the co-ownership for another €6.5 million, making Inter was the sole employer of Icardi in the football field.

On 20 August 2014, in Inter’s first match of the season against Iceland’s Stjarnan for first leg of play-off round of the 2014–15 Europa League, Icardi opened a 3–0 away win. That was his first European goal, in his European debut. In the returning leg, he came in as a second-half substitute and scored two times in a 6–0 win at the San Siro, to advance his team into the group stage 9–0 on aggregate.

Speaking of Icardi, Inter coach Stefano Pioli stated that Icardi “is an animal in the box”, and “always finding the right position”, while the 1982 FIFA World Cup winner Paolo Rossi described Icardi as a “deadly striker”, adding that “even in the most complicated games he can create the right opportunity and take advantage of it.” Inter manager Luciano Spalletti called him “a complete striker” adding that “for his age shoulders so much responsibility”. In an interview in January 2015, Icardi said his role model is Gabriel Batistuta, but during his time at Barcelona, he added that the forward he mostly resembled was Samuel Eto’o.

Icardi is of Italian origin through his paternal ancestors named Icardi from Piedmont and Da Mezan from Venice. He has an Italian passport. He features on the cover of the Italian version of EA Sports’ FIFA 16, alongside global cover star and compatriot Lionel Messi. On 6 December 2015, Icardi was robbed of his £29,000 Hublot watch after Inter’s 1–0 win over Genoa.

On 6 January 2016, Icardi finished Ivan Perišić’s cross from close range for the only goal away against Empoli, putting Inter on top of Serie A. A month later, on 3 February, he scored his 50th Inter goal in all competitions in a 1–0 home win over Chievo, returning Inter to its winning ways after four consecutive matches. In February 2016, it was reported by several newspapers that Inter had rejected a €30 million bid from Manchester United to sign Icardi. On 9 April, he scored his 50th Serie A goal in a 1–0 away win over Frosinone, making his 100th Inter appearance in the process.

In April 2016, Icardi was excluded from Gerardo Martino’s preliminary squad for the Copa América Centenario, although the Argentine manager later named him to Argentina’s preliminary under-23 squad for the 2016 Summer Olympics in Rio de Janeiro. However, Inter did not release Icardi to participate in the Olympics.

In October 2016, rumours started to speculate in Argentina that Lionel Messi was behind Icardi’s exclusion from the national team due to his friendship with Maxi López, his wife’s former partner. The national team coach Edgardo Bauza stated that Icardi’s off-field antics have nothing to do with him not being selected for Argentina and he would receive a call-up soon, adding that Messi does not “dictate” the team. However, he was omitted again for the 2018 FIFA World Cup qualification matches against Brazil and Colombia in November.

On 11 October 2016, Icardi released his autobiography called Sempre Avanti (Always Forward) published by Sperling & Kupfer. The book caused controversy as Icardi had described an incident which offended certain Inter fans, leading to a banner being displayed calling for Icardi to leave the club. He was fined by the club and was forced to remove that chapter from the book.

On 15 January 2017, in the 3–1 home win against Chievo which was the fifth consecutive win in league, Icardi scored his 15th league goal of the season becoming the first Inter player to score at least 15 goals in three consecutive seasons since Zlatan Ibrahimović and Christian Vieri. On 12 March, he scored a hat-trick against Atalanta, bringing his tally to 20 goals for the season. Icardi amassed 24 league goals in 34 appearances in the 2016–17 season, setting a new personal best. In Europa League, he scored twice in five matches as Inter finished last in Group K.

On 19 May 2017, Icardi received his first call-up after more than three years by newly appointed coach Jorge Sampaoli for the friendlies against Brazil and Singapore in June.

In May 2018, Icardi was named in Argentina’s preliminary 35-man squad for the 2018 FIFA World Cup in Russia. Later that month, however, he was left out from the final 23.

Icardi scored his first senior international goal on 20 November 2018, in a 2–0 friendly home win over Mexico. His goal, scored after just 71 seconds, was the fourth quickest goal in Argentina history. In this match, he won the first trophy with the senior team – Copa Adidas 2018.

Icardi made his 200th Serie A appearance on 24 November by playing in the last 13 minutes of a 3–0 home win over Frosinone. On 13 February 2019, because of several comments that Icardi’s wife, Wanda Nara, made about Inter’s management and its players on the TV program Tiki Taka, Inter announced that he was to be replaced by Samir Handanović as club captain. In response to being stripped of the captaincy, Icardi refused to play in the club’s UEFA Europa League match against Rapid Wien the following day.

In July 2019, it was announced that Icardi would not travel on the club’s pre-season tour. On 8 August 2019, the club signed Belgian striker Romelu Lukaku; the following day he was assigned the number 9 shirt that had been worn by Icardi since his arrival in 2013. To avoid potential legal complications, on 20 August Inter assigned Icardi with the number 7 shirt.

On 2 September 2019, Icardi joined French club Paris Saint-Germain on a one-season loan deal with a €70 million option to buy. He made his debut for PSG off the bench in their 1–0 win against Strasbourg on 14 September. On 1 October, he scored his first goal for the club in a 1–0 away win over Galatasaray, in the UEFA Champions League. On 5 October, he scored his first goal in Ligue 1 in a 4–0 home win over Angers. Icardi scored a brace against rivals Marseille on 27 October in a 4–0 win. He got his first hat-trick for the club on 8 January 2020, in a 6–1 win over Saint-Étienne in the Coupe de la Ligue.

In May 2019, Icardi was included in Argentina manager Lionel Scaloni’s preliminary 40-man squad for the 2019 Copa América. Later that month, however, he was excluded from the final 23-man squad for the tournament.

Icardi missed the first two matches of the season, which were against Lens and Marseille, due to having tested positive for COVID-19. He made his return to action on 16 September 2020, in a 1–0 win against Metz, and scored his first two goals of the season in a 0–2 win against Reims on 27 September 2020. In October 2020, PSG manager Thomas Tuchel announced that Icardi had suffered an injury to the internal ligament of the knee.