Pope Francis is on his way to the United States, having departed Cuba Tuesday afternoon.

Following a farewell ceremony at Antonio Maceo International Airport in Santiago, Francis waved to worshippers before slipping into the papal plane, en route to Washington, D.C.

He was scheduled to arrive at 4 p.m. at Joint Base Andrews, where President Barack Obama, first lady Michelle Obama, Vice President Joe Biden and his wife, Jill, are to greet him.

See alsoComplete coverageInteractiveYour messages to the popeSee alsoPope's visit: Follow along at News 12

Earlier Tuesday, Pope Francis celebrated Mass in El Cobre at the most sacred Catholic shrine on this Communist-led island nation, telling the faithful to live a "revolution of tenderness."

The pope entered the Minor Basilica of the Virgin of Charity of El Cobre about 7:45 a.m., preceded by a line of priests and bishops as incense wafted through the steamy morning air.

The jam-packed, cream-colored church topped by a red dome erupted in applause as the pope walked up the center aisle to the altar.

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Worshippers said they were thrilled Pope Francis had come to celebrate Mass and honor the patron saint of Cuba. He is the second pope to visit the sanctuary -- Pope Benedict XVI also came in 2012.

"For me it is a great honor," Humberto Hervella Mateos, 23, said in Spanish. "For me the Virgin of Charity is the mother of Jesus."

In his homily, Francis told the crowd that "generation after generation, day after day, we are asked to renew our faith. We are asked to live the revolution of tenderness as Mary, our Mother of Charity, did. We are invited to 'leave home' and to open our eyes and hearts to others."

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"Our revolution," he continued, "comes about through tenderness, through the joy which always becomes closeness and compassion, and leads us to get involved in, and to serve, the life of others."

He called on people to visit "the sick, the prisoner and to those who mourn."

It was a theme the pope has struck throughout his visit to Cuba: overcoming ideologies to ensure the focus of people's lives is serving others. He has made what some analysts called subtle challenges to the Cuban government to alter its ways.

"It's very clear his message to this regime is: You need to change. We'll work with you, but you need to change," said John Allen, a longtime Vatican analyst and the author of nine books on the Vatican.

Francis "wants to encourage the transformation of Cuba," Allen said, helping to preserve what he likes about the Cuban Revolution -- assisting the downtrodden, for instance -- and eliminating what he doesn't, such as police state repression.

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The Mass came on the final day of Francis' three-day visit to Cuba.

The Minor Basilica of the Virgin of Charity of Cobre is considered the most important church in Cuba. The faithful come from around the country to pray to the virgin, and often ask for "favores" -- favors, or intercessions, to help with problems or meet other challenges in their lives.

They ask for help in overcoming illnesses they or relatives suffer, in getting into the university, or even for success in sporting events. In return, they make a promise to return the favor to the virgin if their wish is granted. They bring back food, candles, money and other things and leave it at the church.

Some promise to climb the long series of steps leading up to the basilica on their knees.

Hervella Mateos said his mother came to the basilica and prayed that she could become pregnant after a decade of trying unsuccessfully. Not long after, she got the good news -- and Hervella Mateos, her only child, was born.

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She repaid the virgin by bringing her son's first set of clothes to the basilica after he outgrew them.

Years later, Hervella Mateos himself prayed to the virgin that he would get a spot in the university -- and he did.

When he comes to the basilica, "I feel close to God," he said.

Another worshipper, Omar Caboverde Rodriguez, 62, said he often travels from his home in Guantánamo to pray to the virgin. His wife was recently diagnosed with diabetes, so now he is asking the virgin to cure her, or at least keep her healthy.

"Since we were children they taught us to love the virgin and have faith in her," Caboverde Rodriguez said in Spanish. "Whenever we have a problem we ask that she help us, that she take care of us."

The basilica is located several miles outside the city of Santiago of Cuba, which is considered the cradle of the Cuban Revolution that brought Fidel Castro to power on Jan. 1, 1959.

He and other guerrillas descended from the Sierra Madre mountains surrounding Santiago and attacked the Moncada military barracks on July 26, 1953. The attack failed and Castro was jailed for a time, but his revolutionary movement was launched.

Bullet holes still pock the walls of the Moncada barracks, which is a museum today honoring the Cuban Revolution.

In his homily, Francis said the Catholic Church should continue to "build bridges, to break down walls, to sow seeds of reconciliation."

Just as the pope's historic visit drew legions of followers into Cuba's streets to get a glimpse, God's presence too "calls us out of our house," Francis said.

Standing before an altar adorned with white, pink and blue roses, the Cuban flag, and the shrine of the Mary holding baby Jesus in her arms, Francis recognized Mary's "maternal presence" in Cuba. He credited Cuban women for keeping the Catholic faith alive "amid suffering and privation."

Hundreds of worshippers -- most dressed in white and many fanning themselves -- gathered in the 89-year-old church to hear Francis' words. Many more gathered outside, sitting on plastic patio chairs and shading themselves with white caps as they watched the Mass on a giant video screen.

"Like Mary, we want to be a Church which can accompany all those 'pregnant' situations of our people, committed to life, to culture, to society, not washing our hands but rather walking with our brothers and sisters," Francis said. "This is our most valuable treasure [Cobre], this is our greatest wealth and the best legacy we can give: to learn like Mary to leave home and set out on the path of visitation."

At the conclusion of the Mass, Francis thanked worshippers for praying for him, and said he wished each of them would get "what they most need." After exiting the church, he stopped to briefly address and give his blessing to the crowd gathered outside.

Francis later waved from his bulletproof-glass enclosed vehicle to worshippers lining the streets of Santiago.

At his final scheduled stop in the country, Francis arrived at Our Lady of the Assumption Cathedral, where he met with families from the nation's second-largest city.

Francis likened the meeting to "the cherry on the cake."

"Thank you, Cuban families. Thank you, Cubans, for making me feel part of a family, for making me feel at home, in these days," Francis said, according to an official transcript of his comments.

The Pope spoke of the warmth with which he was received during his trip, including from a married couple that shared with him their "hopes and struggles" in trying to practice their faith at home.

Francis said routine family gatherings, like weddings and dinners, serve as opportunities to come closer to God.

"In many cultures today, these spaces are shrinking, these experiences of family are disappearing, and everything is slowly breaking up, growing apart," Francis said. "We have fewer moments in common, to stay together, to stay at home as a family. As a result, we don't know how to be patient, we don't know how to ask permission or forgiveness, or even to say 'thank you,' because our homes are growing empty. Empty of relationships, empty of contacts, empty of encounters."

For people concerned with the "kind of world we want to leave our children, the kind of society we want for them," Francis said it should be one built on the bond of family.

"No doubt about it: the perfect family does not exist; there are no perfect husbands and wives, perfect parents, perfect children, but this does not prevent families from being the answer for the future," Francis said.

Concluding his message, the pope asked worshippers to "pray in a particular way" for two upcoming events he will participate in, the World Meeting of Families and the Synod of Bishops devoted to family.

With Jennifer Barrios