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Standing on the tarmac of Havana's Jose Marti airport, Francis called the resumption of full diplomatic ties between the United States and Cuba this year an "example of reconciliation for the entire world."
The pope wrote a personal appeal to Presidents Barack Obama and Raul Castro and hosted their delegations at a secret meeting at the Vatican last year to seal a deal after 18 months of closed-door negotiations. Since then, the two leaders have reopened embassies in each other's countries, held a personal meeting and at least two phone calls and launched a process aimed at normalizing ties in fields ranging from trade to tourism to telecommunications.
Standing with Cuba's president by his side, Francis said the developments over recent months have given him hope.
"I urge political leaders to persevere on this path and to develop all its possibilities as a proof of the high service which they are called to carry out on behalf of the peace and well-being of their peoples, of all America, and as an example of reconciliation for the entire world," he said.
Castro blasted the U.S. trade embargo on Cuba as "cruel, immoral and illegal" and called for it to end. But he also again thanked the pope for his role in fostering "the first step" in a process of normalizing relations.
The Vatican has long opposed the embargo on the grounds that it hurts ordinary Cubans most. On the eve of the visit, the Vatican No. 2, Cardinal Pietro Parolin, made clear the Holy See hopes the rapprochement will eventually result in the lifting of sanctions. The Obama administration also called on Congress to lift the embargo, and on Friday it unveiled a new round of executive actions that carve out exceptions to the sanctions, such as allowing U.S. businesses to open offices in Cuba, letting U.S. residents send unlimited cash to Cubans and permitting virtually all U.S. pleasure boats to travel to the island without a special license.
In his remarks, Francis gave a friendly greeting to Fidel Castro, asking his brother Raul to send the 89-year-old revolutionary "my sentiments of particular respect and consideration."
In the same breath, Francis also gave an apparent nod to Cuban dissidents, who have complained that he wouldn't be sitting down with them during his visit. He said he wanted to embrace "all those who, for various reasons, I will not be able to meet" - as well as Cubans elsewhere in the world. The Vatican spokesman said the pope's words were certainly meant as an expression of greeting to all Cubans, dissidents included.
"This visit is like a breath of hope blowing over Cuba," because of the role that the pope played in the reestablishment of relations with the U.S., retiree Diego Carrera said.
Francis has been on record criticizing Cuba's communist - and for decades atheist - revolution as denying individuals their "transcendent dignity." But like the last two popes to visit Cuba, Francis has no meetings with dissidents on his official schedule. His speeches here are being closely watched for their handling of two delicate and related topics: human rights in Cuba and the church's freedom to operate in the now officially agnostic state.
The pontiff didn't explicitly mention human rights in his speech but said he would pray to Cuba's patron saint, the Virgin of Charity of El Cobre, "for all her Cuban children and for this beloved nation, that it may travel the paths of justice, peace, liberty and reconciliation."
While he made no reference to the church's desire to be allowed to operate religious schools and broadcast on state-run television and radio, he said his trip was to help the church "support and encourage the Cuban people in its hopes and concerns, with the freedom, the means and the space needed to bring the proclamation of the kingdom to the existential peripheries of society."
The Cuban government pursued a citywide effort to bring crowds into the streets of the capital, offering a day's pay, snacks and transportation to state workers to gather along the pope's route from the airport to the papal ambassador's home. University students were also recruited to turn out.
The Vatican estimated more than 100,000 people lined the streets on Francis' route to the residence, where he is staying in Havana. He was greeted with shouts of "Francis! Brother! Now you are a Cuban!"
Francis greeted a specially selected group of Cubans outside the residence Saturday night before a busy first full day on Sunday, starting with Mass in Revolution Plaza followed by a closed meeting with Raul Castro and a possible luncheon with Fidel Castro. The afternoon brings a vespers service and Francis' first encounter with Cuban young people.
Accountant Magaly Delgado said she would go to the Mass because "I'm a believer and this pope interests me a lot because of all the change that he's making."
On Monday, the pope flies to the eastern city of Holguin - part of the periphery that is such a concern for Francis - to celebrate Mass and then on to the far eastern city of Santiago. He spends the night there and celebrates a major Mass at the sanctuary of Cuba's patron, the Virgin of Charity of Cobre, before flying Tuesday to Washington.
He will be greeted at Andrews Air Force Base by the first family. He will then, like his predecessors, grab the world stage at the United Nations to press his agenda on migration, the environment and religious persecution.
The U.S. visit, planned well before the Cuban stop was added, will be notable for the center stage Francis is giving Hispanics, who make up about 38 percent of adult Catholics in the U.S., according to the CARA research center at Georgetown University.
Francis will deliver most of his speeches in his native Spanish and is expected to make immigration one of the major themes of the visit. He has called for countries to be more welcoming of migrants seeking a better life for themselves and decried in particular the plight of would-be migrants crossing the U.S.-Mexico border- signaling he has no qualms about wading into a politically charged issue in the U.S. presidential campaign.
Associated Press writers Eduardo Castillo and Anne-Marie Garcia in Havana and Christine Armario and Andrea Rodriguez in Holguin, Cuba, contributed to this report.