"Today, after 45 long days, I finally returned home," the 86-year-old billionaire media mogul said in a statement after leaving the San Raffaele Hospital earlier in the day.
He described it as "an incredible emotion, a great relief", adding: "It was a distressing and difficult period, but after the darkness, I won again."
In a typically impassioned statement, Berlusconi thanked God and all those who had supported him. "I never felt alone," he said, adding: "The nightmare is over... Long live life, always!"
The senator, who has been plagued by health issues in recent years, was admitted to the San Raffaele on April 5 and spent the first week and a half in intensive care.
Doctors said he had been admitted for treatment for a lung infection, before revealing for the first time that he had leukaemia.
Italian Prime Minister Giorgia Meloni, whose governing coalition includes Berlusconi's right-wing Forza Italia party, led the congratulations for his return home.
"Go Silvio!" she tweeted, adding: "We are waiting for you in the field, to fight many battles together."
Berlusconi led Italy three times between 1994 and 2011 but has dominated public life for far longer, as a businessman and media magnate and through his ownership of the AC Milan football club.
His career has also been dogged by scandal and legal woes, which for the past decade were focused on proceedings relating to his notorious "Bunga Bunga" sex parties.
'Dangerous pneumonia'
Meloni had visited Berlusconi in hospital on Sunday, saying afterwards he had been "in an excellent mood" and was still working "tirelessly".
The former premier also received visits from his Forza Italia deputy, Foreign Minister Antonio Tajani, and coalition ally Matteo Salvini, leader of the anti-immigration League party.
"Welcome home, Great Silvio," Salvini tweeted, while Tajani added: "We're all happy you've returned home."
Berlusconi had hoped to be discharged from hospital earlier this month in time for a Forza Italia convention in Milan but ended up addressing delegates in a pre-recorded video address filmed in his hospital room.
Smartly dressed and sitting behind a desk with his party's banner and the Italian flag behind him, he thanked members for their support, "which more than anything helped me overcome a very dangerous pneumonia".
Despite remaining president of Forza Italia, Berlusconi is rarely seen in public these days, and his health has long been a concern.
He was in hospital for 11 days for Covid-related pneumonia in September 2020, after contracting the virus while on holiday in Sardinia.
He described it as "perhaps the most difficult ordeal of my life" but added: "Once again, I seem to have got away with it!"
After being admitted again last month, doctors revealed that he had "chronic myelomonocytic leukaemia", a rare type of blood cancer.
The disease, which affects mainly the elderly, starts in blood-forming cells of the bone marrow and goes on to invade the blood.
Berlusconi's cancer was in a "persistent chronic phase" and had not yet turned into "acute leukaemia", the doctors said.
In March, Berlusconi was admitted to the same Milan hospital where he spent four days.
