[4] Del Potro's biggest achievement was a major title at the 2009 US Open, where he defeated Rafael Nadal and the five-time defending champion Roger Federer en route.

[11] Del Potro's talent was discovered by Italian ex-tennis professional Ugo Colombini, who accompanied him through the initial phases of his young career, and is still today his agent and close friend.

As a junior in 2002, del Potro won the Orange Bowl 14s title, beating Marin Čilić en route to a victory over Pavel Tchekov in the final.

[27] Later, seeded seventh, he won the Copa Club Campestre de Aguascalientes by defeating the likes of Dick Norman and Thiago Alves, before beating Sergio Roitman in the final.

[31] In Spain, he participated in the Open Castilla y León Challenger tournament held in Segovia, defeating top seed Fernando Verdasco in the quarterfinals and Benjamin Becker in the final.

[14] Del Potro began the year by reaching his first semifinal in ATP Adelaide, Australia, where he lost to Chris Guccione, having beaten Igor Kunitsyn earlier in the day.

[39] Del Potro went further in the Miami Open, reaching the fourth round, after he defeated three top-50 players: Jonas Björkman, Marcos Baghdatis, and Mikhail Youzhny, before falling to Rafael Nadal in two sets.

[82] This left del Potro's qualification for the 2008 Tennis Masters Cup out of his hands, but Jo-Wilfried Tsonga beat James Blake in the semifinals, which was enough to ensure his place at the year-end event.

[88] Nonetheless, del Potro enjoyed a successful season; winning four titles and finishing 2008 as the youngest player in the top 10,[14][27] top-ranked Argentine, and highest-ranked South American.

[106] In the Davis Cup quarterfinal against the Czech Republic, del Potro won his matches against Ivo Minář and Berdych in straight sets, but Argentina still lost the tie 2–3.

[158] Del Potro's next scheduled tournament was the U.S. National Indoor Championships, where he was accepted into the main draw via a wildcard, losing to top seed and eventual champion Andy Roddick.

[169] Del Potro reached the fourth round at Wimbledon for the first time by defeating Flavio Cipolla, Olivier Rochus, and Gilles Simon but lost in four sets to world No.

[201] Less than two hours after this marathon, del Potro took to the tennis court again with Gisela Dulko for their quarterfinal mixed doubles match against Lisa Raymond and Mike Bryan, which they lost.

[205] Del Potro ended the illustrious career of American tennis star Andy Roddick, retiring him by winning their fourth round match before going on to lose in the quarterfinals of the US Open against Djokovic.

The next month, he won the Rotterdam Open, beating Gaël Monfils, Ernest Gulbis, Jarkko Nieminen, Grigor Dimitrov in the semifinals, and Julien Benneteau in the final.

[212] At Dubai, del Potro beat Marcos Baghdatis, saving three match points, Somdev Devvarman, and Daniel Brands, but lost in the semifinals to eventual winner Novak Djokovic.

[217] At Wimbledon, Del Potro won against Albert Ramos, Jesse Levine, and Grega Žemlja before advancing past the fourth round for the first time in his career, thanks to a win over Andreas Seppi.

[218] Del Potro won the Washington Open, beating Ryan Harrison, Bernard Tomic, Kevin Anderson, Tommy Haas in the semifinals and John Isner in the final in three sets.

[221] At the Japan Open, Del Potro, who entered the tournament on a wildcard, beat Marcos Baghdatis, Carlos Berlocq, Alexandr Dolgopolov, Nicolas Almagro and Milos Raonic in two sets to win his third title of the year.

[222] In October, Del Potro reached the final of the Shanghai Rolex Masters, defeating Philipp Kohlschreiber, Tommy Haas, Nicolás Almagro, and Rafael Nadal (for the first time since the semifinals of the 2009 US Open) en route, but eventually losing to defending champion Djokovic in a third-set tiebreak.

[227][228] Del Potro began his 2014 ATP World Tour season at the Sydney International as the top seed, winning the final of the tournament against defending champion Bernard Tomic in only 53 minutes.

Del Potro played in his first gold medal match against the reigning Wimbledon champion from the previous month, Andy Murray and lost in four grueling sets in over four hours.

[269] Del Potro was given a wild card into the Stockholm Open and beat John Isner, Nicolas Almagro, Ivo Karlovic, Grigor Dimitrov and Jack Sock to win his first title since his return from injury.

[280] Del Potro began his clay-court season at the Estoril Open, where he beat Yuichi Sugita for the loss of just four games in the first round, but withdrew the next day after he heard that his grandfather had died.

[286] In May at Lyon Open, del Potro defeated lucky loser Quentin Halys, but lost in the next round against Portuguese qualifier Gastão Elias in straight sets.

[317] Del Potro continued his successful run at the Miami Open, beating Robin Haase, Kei Nishikori and Filip Krajinović, before prevailing in a grueling match against Milos Raonic, reaching the semifinals.

[327] At Wimbledon, Del Potro defeated Peter Gojowczyk, Feliciano Lopez and Benoît Paire, before a long four set win over 2 days against Gilles Simon.

[346] In his first grass-court tournament of the season at Queen's Club, del Potro suffered another career-threatening injury when he fractured his kneecap in his first round match against Denis Shapovalov.

Since his return in 2016, del Potro made tactical changes in his game in order to protect his wrist, like significantly reducing the pace of his two-hander and adopting a one-handed slice.

[383] However, during Argentina's Davis Cup semi-final tie against Great Britain, del Potro got revenge by beating Andy Murray in a five-set thriller that was, for each man, the longest match of his career.