Police arrested the 25-year-old as he flew his drone over the main Via della Conciliazione that leads towards Saint Peter's Square where the pope was leading Sunday prayers.
“He was given an order to leave the country and his drone and camera confiscated,” Rome police said in a statement.
The South African embassy declined to comment his arrest and expulsion. Under Rome's strict security measures, it is illegal to overfly the city, including with a drone.
Two French tourists flying a drone near the Colosseum last year were fined around 3,000 euros ($3,500) and had their equipment confiscated and destroyed, police said.
Violating Italian aviation rules is an offence potentially punishable with fines of up to €113,000.
Another tourist was fined in 2016 after his camera drone crashed into Venice's iconic St Mark's Square.
“Tourists are often caught flying drones,” a spokesperson for the Italian Civil Aviation Authority, Enac, told The Local.