The 88-year-old pope, who also made his first public appearance since February 14 before being discharged from Rome's Gemelli hospital, left the facility shortly after noon.
A car carrying the pontiff was accompanied by police vehicles through Rome, making a short detour at the Basilica of Saint Mary Major, where Francis has a special devotion and visits frequently.
Though the pope has returned from hospital, his doctors have said it would still take "a lot of time" for his ageing body to heal fully.
They have prescribed a further two months of rest at the Vatican and told the pope to avoid large or stressful meetings, leaving unclear how much activity Francis will undertake in the coming months.
Just before leaving the hospital on Sunday, Francis smiled and waved at a group of well-wishers gathered outside. He used a wheelchair, as he has for several years.
His face looked swollen and there were bandages visible on both arms underneath his white cassock.
The pope appeared only for a few moments. He spoke briefly, with a feeble voice, to thank 79-year-old Carmela Vittoria Mancuso in the crowd below. Mancuso, who visited the hospital each day during the pope's treatment, had brought yellow flowers for him.
Francis had only been seen by the public once before during his hospital stay, in a photo the Vatican released last week, showing the pontiff at prayer in a hospital chapel.
The pope, who has been receiving oxygen to help him breathe throughout his hospital stay, was breathing on his own during the public appearance. But he was seen using a small hose under his nose for oxygen while travelling in his car.
In the moments before the pontiff's appearance on Sunday, the crowd of hundreds of well-wishers called out for him, chanting "Francis, Francis, Francis".
THANKS DOCTORS FOR 'TIRELESS CARE'
Francis usually greets people in St. Peter's Square each Sunday at noon and offers a brief prayer. He has not been able to do so since February 9, before he entered hospital.
While the pope did not offer the usual weekly prayer during his public appearance on Sunday, the Vatican released a text that it said was prepared by the pontiff.
"In this long period of hospitalization, I have had the opportunity to experience the patience of the Lord, which I also see reflected in the tireless care of doctors and healthcare workers, as well as in the devotion and hopes of the families of the sick," the text said.
Many Catholics around the world had been praying for the pope's recovery. Pilgrims at the Vatican on Sunday expressed relief at his leaving hospital.
"This discharge cheers us all up and gives us joy and hope," said Grazia Mara, an Italian. "We wish him a safe return home and a speedy recovery."
The pope had continued leading the Church from hospital.
He was making usual appointments of Catholic bishops around the world and also launched a new three-year reform process for the global institution.
But a period of two months rest for Francis could lead to significant changes to the Vatican's calendar of coming events.
The pope had been set to meet with Britain's King Charles on April 8 and to lead the Vatican's annual Easter celebrations on April 20.
The Vatican has not said whether Francis will be able to keep those appointments.
