The pope may also talk about mental health, particularly when visiting the Casavalle neighborhood in Montevideo, which is notorious for high levels of poverty and extreme violence.
The tour is seen as something of a homecoming for the pontiff, who lived in Peru for almost two decades and holds joint U.S. and Peruvian citizenship.
The visit combines pastoral stops with places tied to his years in Peru and to social conditions in Uruguay's capital.
His mail-in ballot made history as he was the first pope ever known to vote in a political election.
Casavalle's reputation for poverty and violence frames possible remarks on mental health during the Montevideo portion of the trip.
Leo spoke to reporters including AFP on the flight into Uruguay as he opened the regional journey.
Callao's statue marks the Peruvian city on the itinerary after the Uruguayan opening.
A towering 14-metre (46-foot) statue of Leo has been erected in the port city of Callao, which he is to visit.
He said he wanted to bring a message of hope in today's world. The leader of the world's 1.4 billion Catholics also said he was in fairly good shape following his surgery. I'm proud to be an American and to exercise the right to vote, he said.