The pontiff's plane lifted off about 7:30 p.m. local time following a brief ceremony that concluded his weeklong trip to Brazil for the Catholic Church's World Youth Day, the Los Angeles Times reported.
The 3 million people who attended the worship service earlier in the day made it one of the largest papal masses in recent history, the newspaper noted.
"Do not be afraid to go and to bring Christ into every area of life, to the fringes of society, even to those who seem farthest away, most indifferent," Francis told the sea of humanity that covered the expansive Copacabana beach.
"There are no borders, no limits: He sends us to everyone."
Brazilian President Dilma Rousseff and leaders of Argentina -- Francis' homeland -- and Bolivia were among the throngs who attended the mass, the Times said.
Millions also had flooded the beach Saturday night for a vigil, organizers said. Many of the pilgrims then slept in the sand, the BBC reported.
During the vigil, the pontiff stood on a large stage and exhorted young people to work to change society for the better and to rebuild the Catholic Church, which has experienced an exodus of members in recent years, the BBC said.
"The young people in the street are the ones who want to be actors of change. Please don't let others be actors of change," he told the massive audience.
"Keep overcoming apathy and offering a Christian response to the social and political concerns taking place in different parts of the world."
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