Chronic violence and corruption will be themes of his visit to the world's second most populous Roman Catholic country, and he will address the plight of migrants trying to reach the United States with a service at the northern border next week.
Hundreds of thousands of people are expected to join the pope on Saturday afternoon at the Basilica of Our Lady of Guadalupe, where pilgrims flock from all over Latin America.
‘'Don't be afraid,' that is what she tells me,’ the Argentine-born pontiff said ahead of his visit, adding that he wanted to reflect silently in front of her image.
Carrying pictures of the pope and the Virgin of Guadalupe, wrapped up against the winter chill, thousands converged on Mexico Citys historic center, where the pope is set to address the government at President Enrique Pena Nietos ceremonial palace.
‘This country needs (the popes) blessing. Were really struggling with corrupt politicians, unemployment, drug gangs and everyone knows it,’ said Juanita Lopez, a 58-year-old maid, as she walked to the Zocalo, the capitals main square, clutching a rosary.
The pope earlier this month urged Mexicans to fight against corruption and brutal drug gang violence. Some Mexicans are looking to him to take that even further while he's here.
‘We want him to demand that the president kick out all the corrupt people,’ said Marbella Vargas, whose son Edgar was one of 43 students abducted and apparently massacred in 2014, a grisly case that hammered the government's reputation.
Mexico has been ravaged by drug violence over the past decade, and Pena Nieto has been unable to fulfill his promises to put an end to it.
The pope flew into Mexico City on Friday evening for his first visit as leader of the Catholic Church, greeted by cheering crowds, a mariachi band and Pena Nieto.
During his visit, the pope will say Mass with indigenous communities in Mexico's poorest state Chiapas, and speak with young people in Morelia, the capital of Michoacan state that has been plagued by violence between drug gangs and armed vigilante groups.
More than 100,000 people have been killed in Mexico's drug violence over the last decade and some 26,000 are missing.
The pope's trip will end with a prison visit and Mass in the notorious northern border city of Ciudad Juarez, where he will meet relatives of victims of violence.
In a reminder of Mexico's corruption and violence, 49 people were killed in a fight between rival gangs in a prison just days before the pope's arrival.
There has been speculation that the pope might also meet with relatives of the 43 missing students.
Francis, the first pope from Latin America, has won plaudits for his leadership of the Church over the last three years. But in Mexico he may struggle to match the lasting appeal of Pope John Paul II, who made multiple visits to the country.
More than half of those polled by newspaper Reforma last month said they identified most with John Paul II, versus 14 percent for Francis.