Leo travelled to the port city of Douala, Cameroon's financial and economic hub, on a day dedicated to encouraging the country's youth.
Later on Friday back in the capital, Youande, Leo has an appointment with students, professors and administrators at the Catholic University of Central Africa.
The big field in front of the Japoma sports stadium was bursting with people singing, swaying and dancing as an announcer shouted "Habemus Papam!" (We have a pope!).
The Latin phrase is used to announce the election of a new pope but in this case joyfully announced Leo's arrival at the field.
The crowd cheered when Leo emerged in his open-sided popemobile, with waves of young people running alongside him trying to keep up as he looped through the crowd.
Some had spent the night on the ground, battling mosquitoes, to be in place for the late-morning mass, but said they were willing to make the sacrifice for the Pope.
The Vatican had predicted some 600,000 people would turn out for the liturgy.
But by the end of the mass, the Vatican quoted local organisers as saying about 120,000 attended.
In his homily, delivered in French and English, Leo cited the Biblical story of Jesus' multiplication of loaves in urging young people to "multiply your talents through the faith, perseverance, and friendship".
He urged them to look beyond the poverty and disillusionment many experience and instead look to the future with hope.
"Do not give in to distrust and discouragement," he said.
"Do not forget that your people are even richer than this land, for your treasure lies in your values: faith, family, hospitality and work.
"Do not let yourselves be corrupted by temptations that waste your energies and do not serve the progress of society."
With a population of 29 million, Cameroon is an overwhelmingly young country, where the median age is 18.
Leo has already offered words of encouragement to Cameroon's youth, including in his opening speech to President Paul Biya - at 93 the world's oldest leader.
In the speech, Leo demanded the "chains of corruption" in Cameroon be broken and said Cameroon's youth represented the future and hope of the country.
But with Biya in power since 1982, Cameroon perhaps represents the most dramatic example of the tension between Africa's youth and the continent's many ageing leaders.
Despite being an oil-producing country experiencing modest economic growth, young people say the benefits have not trickled down beyond the elites.
