While speaking from the apostolic window, Pope Francis noticed visitors holding signs that said "have a good trip."
He smiled and thanked the crowd, the Vatican said.
The pope will arrive in Rio de Janeiro Monday, the Vatican Radio said.
The trip was originally planned for Benedict XVI, but Pope Francis has added his own touches.
He insisted on leaving the bulletproof pope mobile at home, and will instead travel in an open-top jeep during his week in Brazil, The Miami Herald said.
The itinerary offers many chances for Pope Francis to mingle with everyday people.
He is set to pray with young people on the beach, talk to young inmates from a prison, and meet with drug addicts at the hospital, the Herald said.
He will also be meeting with local and national politicians and attend World Youth Day events.