The accident occurred shortly before daybreak, on a highway about 50 kilometres west of the Venezuelan capital, said Victor Lira, head of the federal civil protection office.
"So far we have a regrettable toll of 20 dead and 10 people hurt," Lira said.
More casualties were likely, however, given the force of the crash, which ripped away the entire right side of the coach.
Officials said the bus, which had a capacity of 60 seated passengers, was travelling from Lara state to Caracas when the driver lost control, smashed through a traffic median and into a tree along the side of the roadway.