Three experts defused the 500-pound American bomb during a three-hour operation that also forced 60,000 people to stay in their homes and closed sporting complexes and churches, Italian news agency ANSA reported.
The bomb was then taken to a remote location for a controlled explosion.
An alarm signalled the all-clear to reopen the city centre just before midday, as well as a nearby north-south highway and rail line both connecting Italy with Austria and Germany.
The bomb was found in Piazza Verdi, near the city’s main cathedral and not far from the train station — the likely wartime target — during excavation works for a new shopping centre.
Unexploded bombs are common throughout Europe, especially in the UK and Germany.
Around 2000 tonnes of World War II munitions are found in Germany every year.
Just in Berlin, 1.8 million pieces of ordnance have been defused since 1947.
While most of the undiscovered explosives in Italy are believed to be near the border with Austria, in July, 10 unexploded bombs dropped by the Allied Forces were found during an archaeological dig at Pompeii.