A crowded bus has plunged into a river bank in central Vietnam, killing 34 people and injuring 21 others in one of the country's deadliest road accidents.

Local official Tran Bao Que said the bus smashed through the rails of a bridge on Thursday night and plunged into the bank of the Serepok River about 18m below.

The bus was travelling on a regular 350km route from the central highland province of Dak Lak to the southern commercial hub of Ho Chi Minh City.

Y Bliu Arul, deputy director of the general hospital in Dak Lak, said the two drivers of the bus were among the 32 people who died at the scene. Two others died in hospital.

Of the 21 people injured, 16 were said to be in a serious condition.

Que said it took rescuers four hours to pull the bodies from the bus, part of which was submerged in the river.

"When the accident happened, everyone in the bus was sleeping,'' online newspaper Dan Tri quoted survivor Nguyen Van Khanh as saying.

"I vaguely heard a noise like gun fire and then people were screaming when the bus was overturned ... I managed to escape through a window which was smashed opened by others.''

Authorities are investigating the cause of the accident.

Road accidents kill more than 11,000 people each year in Vietnam.