The mural, painted by street artist Mauro Pallotta, depicted the pontiff in a Superman-style flying pose.
It was erased Thursday by street cleaning company AMA, the ANSA news agency reported.
AMA said the mural was treated as graffiti and removed from the wall near Vatican City to preserve the area's "decorum."
Pallotta hinted the mural, which received a positive mention on the Vatican's official Twitter account, could return at a later date. He has been meeting with the owners of a larger building to discuss painting a larger-scale version of his super hero pope, ANSA said.