The blaze in the district of Xuan Loc forced traffic to be closed in both directions for an hour while fire and emergency crews extinguished the flames and removed passengers to safety.
The bus driven by Tran Ngoc Hai caught fire at about daybreak while in route from the city of Binh Thuan to Ho Chi Minh City.
The 45-year-old driver reported hearing a loud noise before noticing the fire, which apparently was caused by an overheated engine. He evacuated his passengers and no one was seriously hurt.
Fire officials said they would investigate the case.