The 46-year-old man reportedly shouted “I’ll kill everyone” while waving a knife and spitting at people at the tourist hotspot in the Vatican City.
Italian newspaper Il Messaggero reported he was wearing a backpack which had eight more knives in it when he was arrested by local police.
The man, who is believed to be French, was arrested and is understood to be being psychologically evaluated while officers determine his motives for the attack.
It comes after a man armed with a long knife killed an several people and injured others in the southern city of Wuerzburg in Germany before being shot by police and arrested.
The Vatican City is an independent enclave within Rome governed by the Pope and is popular with tourists and Catholic visitors.
As well as St Peter’s Basilica it is home to the Sistine Chapel and the Vatican Museum which include art works by the likes of Michelangelo, Raphael and Botticelli.