The 71-year-old walked unaided to his waiting car, stopping to speak to well-wishers outside Rome's Gemelli Hospital.
He stopped to speak to a 13-year-old girl named Varvara from Ukraine who has been in Italy for cancer treatment.
"I am much better, thank you," the Pope said when asked how he was as he was driven away in a black SUV.
His doctors had earlier said he was well enough to return home after they carried out the latest blood tests and chest imaging.
The Pope, who had an operation on Tuesday to remove the lower lobe of his right lung, will hold his first public engagement since surgery on Sunday when he leads weekly prayers with pilgrims in St Peter's Square at noon.
Leo has been diagnosed with lung adenocarcinoma, the most common form of lung cancer.
The diagnosis for a Pope known to be relatively young and energetic and who was elected only in May 2025 caused shock and raised questions about the future shape of his papacy as he deals with the illness.
The Pope's doctors have said his surgery was completed successfully, without complications.
They have not yet disclosed the size of the tumour or whether the disease had spread to nearby lymph nodes, key factors in determining prognosis.
Since the surgery, Leo has shown signs of recovering well.
He had a phone call with Russian President Vladimir Putin, held meetings with senior aides and celebrated Mass in a makeshift hospital chapel.
The call with Putin was to urge him to agree to a ceasefire to help get vital supplies into the Russian-controlled Ukrainian town of Oleshky.
The Vatican had initially estimated a week-long hospital stay and cancelled his audiences through Tuesday.
Experts said patients could be discharged earlier depending on their recovery while Vatican spokesman Matteo Bruni said the decision rested with the Pope's doctors.
The Vatican said work on Leo's November 6 to 17 visit to Uruguay, Argentina and Peru - one of the most intense arranged for a pontiff in decades - was also "going forward".
It released a list of journalists accredited to travel with Leo and cover the trip.
with AP
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