A 50-metre-high section of the bridge, including a tower that anchored several stays, crashed down before 12:00 pm, with as many as 35 vehicles driving on it in torrential rain.
Huge slabs of reinforced concrete plunged onto two warehouses, train tracks and a riverbed.
According to authorities from the Liguria region, the death toll stands at 26, but this number is likely to rise as rescue efforts continue.
An official for the civil protection agency said there had been 30 cars and five to 10 trucks on the section that fell.
Motorist Alessandro Megna told RAI state radio he had been in a traffic jam and seen the collapse.
“Suddenly the bridge came down with everything it was carrying,” he said.
“It was really an apocalyptic scene; I couldn’t believe my eyes.”
Italy’s Autostrade, a motorway operator controlled by Atlantia, said it had been carrying out maintenance work on the flyover bridge.
Autostrade said it had been strengthening the road foundations of the bridge, which had been built in the 1960s.
“The works and state of the viaduct were under constant monitoring and supervision,” the company said in a statement.
“The causes of the collapse will be thoroughly investigated as soon it is safe to access the site.”
Within hours of the disaster, the anti-establishment government that took office in June said the collapse showed Italy needed to spend more on its dilapidated infrastructure, ignoring EU budget constraints if necessary.
We should ask ourselves whether respecting these limits is more important than the safety of Italian citizens. Obviously for me, it is not,” said Deputy Prime Minister Matteo Salvini, head of the right-wing League, which governs with the Five Star Movement.