Pope Francis told indigenous Mexicans that today's world "needs you!", denouncing their systematic exclusion from society and encouraging the use of native languages in Catholic worship.
He was preaching yesterday in the south of Mexico. Parts of the ceremony, which was held in a packed out sports ground in the state of Chiapas, were given in three indigenous languages – Tzeltal, Ch'ol and Tzotzil – and Bibles were distributed in these tongues.
Francis quoted the Popol Vuh, a sacred Maya text, and drew comparisons between Catholic and indigenous values.
"Today's world, ravaged as it is by a throwaway culture, needs you!" he said, referring to the mostly indigenous throngs who loudly cheered him.
"You have much to teach us," he said, lauding Mexico's native peoples while denouncing "the systemic and organised way your people have been misunderstood and excluded from society."
The region, mired in poverty and plagued by rising insecurity, has fallen far behind other parts of the country economically.
Factory worker Alma Gonzalez, 23, who speaks Spanish and Otomi and travelled from the State of Mexico to hear the Pope, was touched he was reaching out to her people.
"I'm indigenous... I want to thank him for paying attention to us, the poor," she said.
The Pope last year apologised for the role of the Church in the conquest of Latin America and left a Vatican decree while in Chiapas authorizing translations of the liturgy into indigenous languages.
The state of Chiapas was the scene of the Zapatista uprising of Maya rebels in the 1990s. It is now the frontline of a government crackdown on illegal immigration to the United States from Central America.
When the Zapatistas burst onto the scene, more than two-thirds of Chiapas' population was Roman Catholic. The expansion of evangelical Christianity through poor indigenous towns since has driven the number down to around 60 per cent, making it Mexico's least Catholic region.
The poverty rate in Chiapas, already the most impoverished state in Mexico, has risen in recent years to more than three-quarters of the population.
Mexico, with help from the United States, has increased patrols on its southern border and is deporting more Central American migrants trying to reach the United States.
Thousands of people from neighbouring Guatemala are believed to have crossed over the porous border of rivers and jungle in Chiapas for a chance to see the Pope.
Today he will speak to young people in Morelia, the capital of Michoacan state, where warring drug gangs cook much of the methamphetamine smuggled into the United States.
He will then travel to Ciudad Juarez, which borders the US state of Texas, where he will pray for migrants and victims of violence.
Additional reporting by Reuters.