At least 20 people, including two children, were killed on Tuesday and several others wounded when a bus running on methane plunged off a bridge in Venice and caught fire.

"A tragedy has struck our community this evening", mayor Luigi Brugnaro wrote on Facebook, describing the site of the crash as "an apocalyptic scene."

The crash caused "at least 20 deaths, including two children," a spokesman from the city hall said.

"At least 10 people have suffered injuries of varying degrees and have been taken to hospital," he said, adding that operations were underway to rescue any others wounded.

Firefighters said the bus caught fire after careering off a bridge straddling a railway line and linking the Mestre and Marghera districts of the northern Italian city.

Italian Prime Minister Giorgia Meloni expressed her "profound condolences."

"I am in contact with mayor Luigi Brugnaro and (Transport) Minister Matteo Salvini in order to follow the news of this tragedy," she said in a statement.

According to Il Corriere della Sera newspaper, the bus swerved off the bridge after smashing through the barrier and fell near railway tracks about 30 metres below.

The newspaper said it caught fire after hitting some power lines.

Interior Minister Matteo Piantedosi said, "The aggravating factor was methane and the fire this spread rapidly."

"I fear that the death toll will rise," he added.

In July 2018, a bus carrying a group of some 50 holidaymakers back to Naples fell off a viaduct near the city killing 40 people in all. (AFP)