The 71-year-old pontiff had been recovering in Rome's Gemelli hospital since undergoing a lung operation on Tuesday.
Pope Leo XIV has reportedly left hospital following surgery to remove a cancerous growth from his lung.
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The AFP news agency reported that the 71-year-old pontiff was met with cheers and applause from people gathered outside the hospital as he made his way out.
He had been cleared for discharge from hospital earlier on Saturday, the Vatican had announced.
"Following the doctors’ assessment this morning, Pope Leo XIV will be discharged today from Gemelli Hospital, where he was hospitalised for surgery on his right lung," a statement from the Vatican press office said.
"He will leave the hospital in the early afternoon and return to the Vatican. Tomorrow, he will lead the Angelus prayer from the window of the papal apartment," it added.
Doctors said the decision had been made after blood tests and a chest X-ray confirmed he was fit to be discharged.
Chicago-born Leo had been recovering in Rome's Gemelli hospital since undergoing the operation on Tuesday.
The Vatican said earlier this week that the "lower lobe of the right lung was removed" during the procedure, whilst also confirming a diagnosis of a "pulmonary adenocarcinoma, as suspected from the pre-operative tests."
"The Holy Father was in the operating room for about 3 hours, and the duration of the operation itself was around 90 minutes. The surgery was successful and there were no complications," it added.
On Thursday, doctors said a chest X-ray had shown "good recovery" of the affected lung.