The coach broke through a barrier on a flyover and plunged almost 50ft near railway tracks in the suburb of Mestre on Wednesday evening before catching fire.
The crash happened shortly before 8pm as the vehicle carrying 39 people made its way to a campsite in another suburb, Marghera.
Three children including a baby were among the dead, emergency services said. Venice prefect Michele Di Bari said that many of the people involved in the accident were “young”.
Interior Minister Matteo Piantedosi said that the toll could rise. Five Ukrainians, one German and the Italian driver were among the dead, officials said.
Fifteen people are known to have been injured, five of them seriously. They were said to have included Ukrainians, Austrians, Spaniards and other foreign tourists.
Venice prosecutors are investigating if the driver felt ill while he was driving. He was said to be an experienced driver.
There was no indication on the road that he had tried to brake before the crash, the BBC reported. Police are studying video from security cameras near the crash site.
Witnesses told Rai TV they could hear people screaming but the flames were too high to intervene.
Mauro Luongo, commander of the Venice firefighters team, said: “The people in the bus found themselves surrounded by flames. The scene we found was terrible.”
The vehicle is reported to have been a hybrid, powered by electric batteries and methane gas.
Italian reports suggest the gas tank exploded on impact and fire brigade commander Mauro Longo told Il Gazzettino website that the batteries caught fire and made the task of clearing the bus a complex operation.
The Veneto region governor, Luca Zaia, told RAI state television that the cause of the accident was still unclear.
“This is an important tragedy, but it’s difficult to understand how it happened,” he said.
The incident is one of Italy’s worst coach crashes. In 2017, 16 people on a bus carrying Hungarian students died in an accident near the northern city of Verona.
In 2013, 40 people were killed in one of Italy’s worst vehicle accidents when a bus plunged off a viaduct close to the southern city of Avellino.