"Dear friends, I begin my visit filled with excitement and hope for the days ahead," the Pope said in a short speech at Mariscal Sucre International Airport.
Francis' weeklong trip will take him from Ecuador to Bolivia and Paraguay. Vatican officials say they expect millions to turn out for Masses led by the Pope. On Sunday, deep crowds lined the roads from the airport in Quito, hoping to catch a glimpse of the popemobile.
"From the peak of Chimborazo to the Pacific coast; from the Amazon rainforest to the Galapagos Islands, may you never lose the ability to thank God for what he has done and is doing for you," the Pope said.
"May you never lose the ability to protect what is small and simple, to care for your children and your elderly, to have confidence in the young, and to be constantly struck by the nobility of your people and the singular beauty of your country."
The Pope's brief remarks followed a lengthy speech by Ecuador's President Rafael Correa, who thanked the pontiff for his strong defense of the environment and noted that his country's constitution is one of the first to grant rights to nature.
Francis thanked Correa for the warm welcome and joked that the President had quoted him too much.
On the Pope's mind: The poor and the environment
On the plane from Rome, Vatican spokesman Rev. Federico Lombardi said that Pope Francis, a native of Argentina, is "excited" to bring his message of hope, concern for the poor and care for the environment to his native continent. It's his first trip to South America since July 2013 when he traveled to Brazil for World Youth Day.
Asked why Francis is not visiting Argentina on this trip, Lombardi said, "Well, there is time, and we know that he is always putting others before himself, before his family and in that sense he begins from the periphery, other people, and to show that he does not have preference or privileged, and he has to be attentive to everyone in the world."
Ecuador, Bolivia and Paraguay are among the poorest nations in South America.
"They are the forgotten countries," said the Rev. Gustavo Morello, a Jesuit from Argentina and professor of sociology at Boston College. "No one knows what is going on there."
The Pope wants to change that, Vatican officials say, as part of his concern for people on the periphery of modern life: the indigenous poor, the land-cramped farmers and the jobless young people vulnerable to crimes such as sexual trafficking.
Shoring up a Catholic South America
Francis also likely wants to breathe new life into a Catholic Church suffering through a continentwide decline, religious experts say.
More than 425 million Catholics live in Latin America, according to a 2014 study by the Pew Research Center. That's nearly 40% of the world's total Catholic population.
But Catholics in nearly every country, including Ecuador, Bolivia and Paraguay, have fled the church in recent decades for other faiths or no faith at all.
"Soon we will find out if there is a 'Francis effect' in his native region in terms of Mass attendance and participation in church life," said Andrew Chesnut, an expert on Catholicism and author of several books on spirituality in Latin America.
Politically, spiritually and perhaps even personally, the trip to Latin America comes at a crucial time for the Pope.
His 22 planned speeches and million-strong Masses will demonstrate where he has taken the church thus far and where he wants it to go.
In addition to celebrating Masses and meeting with heads of state and Catholic clergy, Francis will take side trips to a home for the aged run by Ecuadorean nuns, a meeting of grassroots political activists and one of the continent's largest prisons in Bolivia, as well as a slum and children's hospital in Paraguay.