The bridge, known as Ponte Morandi, is as tall as 100m (328ft) and is part of the A10 motorway connecting the city of Genoa to Savona and Ventimiglia.
Emergency services rushed to the scene following reports of the collapse, which took place at around 11.30am local time (10.30am BST).
Italian ambulance service said there are “dozens of dead”, local news agency Adnkronos reported.
Italy’s Transport Minister Danilo Toninelli called the collapse “an immense tragedy”.
He said: “I’m following with great apprehension what has happened in Genoa, which appears to be an immense tragedy.”
More than 200 firefighters are currently on the scene.
Dramatic pictures show huge sections of rubble on the ground below the mid-section of the bridge.
Ten victims have been confirmed so far, but the death toll is expected to rise.
Not only did the collapse involve dozens of cars on the motorway but also the houses and rail tracks below, which were hit by big chunks of cement.
Francesco Bermano, head of the region’s ambulance service, said: “The size of this disaster is epochal, there are dozens of deaths, including people who fell from the bridge and those who remained trapped underneath the rubble.
“The firefighters and paramedics are working to pull out from the rubbles the victims, some have already been taken to various hospital in Genoa.
“We have received the full support of nearby regions Lombardy and Piedmont, all their hospitals are available to us.
“We are woking but at the moment we still can’t figure out how dramatic the situation really is.”
The missing section of the bridge is dozens of metres in length.
The Italian Police tweeted: “Violent storm in Genoa. Part of the bridge between Polcevera and Morandi at KM 0,200 on the A10 motorway.
“Mandatory slip exit at Genoa airport, Ventimiglia bound.”
Authorities haven’t yet confirmed the cause of the collapse, but Italian newspaper Corriere Della Sera argued the incident may have been triggered by structural failure.
Italian politicians rushed to express their solidarity to the victims and people involved in the incident.
Lega leader and Interior Minister Matteo Salvini said: “We are following minute by minute the situation of the collapse of the bridge of Genoa.
“I thank the 200 firefighters (and all the other heroes) who are already working to save lives.”
Antonio Tajani, president of the European Parliament, also took to Twitter to share his thoughts and prayers.
He wrote: “There are no words for what just happened in Genoa.
“I just talked to @GiovanniToti. Praying.”
Mr Toti is the president of Liguria, the region where the bridge is located.
Davide Ricci, a person who witnessed the disaster unfolding before their eyes told Italian daily La Stampa: “I saw the bridge collapsing before my eyes.
“The debris of the collapsed bridge arrived 20 metres away from my car.
“First the central pillar crumbled, then everything else came down.”
A crisis unit, for any injuries, was set up at Villa Scassi. Rail traffic has been suspended.
Northern Italy is currently being plagued by a torrential rainfall.
MORE TO FOLLOW