The Vatican said in a medical bulletin on Tuesday that doctors had removed the lower lobe of the Pope's right lung.
The diagnosis of lung adenocarcinoma had been suspected by preoperative tests and was confirmed during surgery.
The 71-year-old was in the operating room for about three hours, with the surgery itself taking about 90 minutes.
"The surgery was successful, and there were no complications," the Vatican said in the statement, later adding he had spent a tranquil night in hospital.
Meanwhile, Deborah Prevost, the wife of Pope ‌Leo's 74-year-old sibling Louis Prevost, who lives in Florida, said he was being treated at a clinic for multiple myeloma.
It is a form of blood cancer that affects the bone marrow and the production of blood cells, producing common symptoms and complications including back pain, anaemia and kidney damage.
Speaking with US broadcaster CBS on Tuesday, she said he was first diagnosed in 2017 and underwent stem cell treatment in 2019, after which the disease remained under control for a long time.
She did not provide details about her husband's current condition and did not know how the Pope, whose birth name is Robert Francis Prevost, was doing following his surgery.
The two brothers spoke last week, Deborah Prevost said. "He called to let us know what would be happening," she told CBS.
"We keep praying, keeping spirits up for both of them."
The American pontiff has offered a rare level of transparency about the first publicly disclosed major health problem of his 17-month papacy.
He revealed the discovery of the small, localised nodule during his Sunday noon prayer and announced that he would have it removed.
The Vatican on Monday cancelled all of Leo's audiences through to next Tuesday.
He underwent surgery at Rome's Gemelli hospital, entering through the main entrance and waving to dozens of well-wishers who had gathered to greet him.
The Vatican said the surgery would be performed by a team led by Gemelli's chief thoracic surgeon, Dr Stefano Margaritora.
Before the operation, oncologists said that even if the nodule turned out to be cancerous, Leo's prognosis was "excellent" since it would have been removed at an early stage.
While Gemelli has a specific papal apartment that past popes have used - complete with a private chapel on the 10th floor - it is undergoing renovations so the pontiff is staying in a nearby room, according to the Vatican press office.
There was no word on whether he would be able to keep his planned trip to South America in November.
A lung nodule is a small abnormal area measuring less than three centimetres that sometimes appears on a CT scan of the chest or abdomen.
Often, the scans are done to investigate trauma or a lung infection, unrelated to a lung cancer screening.
A nodule can be benign or malignant, and oftentimes surgical removal is recommended both to establish whether it is cancer and to treat a malignancy while it is still localised.
This is believed to be the second hospitalisation for the pope, who is known to be sporty and in good shape, with weekly tennis games and swimming.
with DPA