Two months later, he reached his first ATP Tour final at the 2018 Swiss Open, where he won his maiden title and made his top 60 debut.

At 1.96 m (6 ft 5 in), Berrettini possesses one of the tour's fastest serves and often uses his heavy topspin forehand to dictate rallies and set up one-two punches, making him versatile on all surfaces.

In order to compensate for his weaknesses, he often deploys his backhand slice to keep the ball low for his opponent and uses a blocked return to neutralize points.

On his next tournament, he entered his first Grand Slam main draw as a lucky loser at Australian Open but lost in the first round to No.

He entered the 2018 BNP Paribas Open as a lucky loser replacing 17th seed Nick Kyrgios directly in the second round.

At the Swiss Open Gstaad, Berrettini won his first ATP title, defeating Roberto Bautista Agut in the final.

[11] At the Hungarian Open, Berrettini won his second ATP singles title, defeating Filip Krajinović in the final.

Berrettini's improvement continued into the grass court season, winning his third singles title in Stuttgart over Félix Auger-Aliassime in the final.

As the 17th seed at Wimbledon, Berrettini reached the fourth round of a Grand Slam for the first time after defeating Diego Schwartzman in five sets.

[17] After withdrawing from the ATP Cup due to physical problems, at the Australian Open, Berrettini beat Andrew Harris before losing to Tennys Sandgren in the second round.

Berrettini's strong performance advanced Italy to the final of the 2021 ATP Cup against Russia, where he lost to Daniil Medvedev in straight sets.

Berrettini remained out of competition until the clay season in April, where he won his first singles title in over a year at the Serbia Open over Aslan Karatsev.

On 20 June Berrettini won the biggest title of his career at the Queen's Club Championships,[20] his first at the ATP 500 level.

He became the first Italian in history to win this title, defeating three Britons en route (Andy Murray, Dan Evans, and Cameron Norrie).

[26] At the Australian Open, Berrettini reached the quarterfinals for the first time after defeating Brandon Nakashima, Stefan Kozlov, Carlos Alcaraz, and Pablo Carreño Busta en route.

[29][30] There, he was stopped by eventual champion Nadal in four sets,[31] but as a result of his run, he improved to a career-high ranking of world No.

Following a poor outing in Rio de Janeiro and an early retirement in Acapulco, he then traveled to Indian Wells, where he was dispatched in the fourth round by Miomir Kecmanović in three sets.

[32] Soon after, Berrettini announced that he had sustained an injury to his right hand that necessitated emergency surgery, forcing him to withdraw from Miami and the tour's clay swing, including the French Open, in order to fully recover.

[33][34] Berrettini returned for the tour's grasscourt season at the Stuttgart Open in early June, and found his form by winning the title.

[42] Berrettini started his season at the inaugural edition of the United Cup, defeating Thaigo Monteiro and Casper Ruud in straight sets.

[43] After that, he played the Mexican Open, defeating Alex Molčan and Elias Ymer, before retiring to Holger Rune in the quarterfinals.

Berrettini started the year by withdrawing from 2024 Australian Open on the eve of his scheduled first-round match against Stefanos Tsitsipas because of a foot injury.

[45] He then held an online press conference on 20 February to announce that he will be back to competition in March after six months of hiatus, starting from the 2024 Arizona Tennis Classic and the 2024 Miami Open and then into the clay season.

[48] In Miami he lost to Andy Murray in three sets in a close-to-three hours match while dealing with intestinal virus, almost fainting at some point.

[52] He lifted his fourth clay title and first since 2022, defeating defending champion Roberto Carballes Baena in straight sets.

[55] However, he later withdrew from Madrid, Rome and Roland Garros revealing he is not quite ready after recovering from illness, missing these tournaments for three consecutive years.

[68] Berrettini focuses on setting up quick points and hitting winners with aggressive play and putting pressure on his opponent.

His aggressive game grounded in big serves and forehands have led to many to compare him to Fernando González and Juan Martín del Potro.

In August 2023, Hugo Boss launched its new collection, featuring Berrettini, Patrick Mahomes, Naomi Campbell, Suki Waterhouse, and Lee Min-ho in its campaign.