Police said the bus left Phuket on Tuesday evening bound for Bangkok.
Police said the fatal accident occurred on Phetkasem road in tambon Tha Sae or Tha Sae district about 2.30am Wednesday.
The bus was found overturned in a ditch separating the opposing lanes, its windshield and front end smashed in.
Police said 13 Thai and eight foreign passengers suffered cuts from broken glass and concussions from falling belongings. They were promptly taken to nearby hospital and most had already been released.
The bus driver was found stuck in the wreckage. Emergency workers spent more than 30 minutes cutting through the twisted metal wreckage to pull him out. He was later identified as Paisarn Varasin, 50, a Pathum Thani native. Mr Paisarn suffered a severe head injury and body wounds. Attempts to resuscitate him failed and he died at the scene.
Four-year-old Jirawat Photibata was also found dead in the wreckage.
The bus driver was said to be travelling at speed when he saw an accident about 200 metres ahead involving a 10-wheel truck and a pickup truck. He apparently panicked and swerved the bus into the ditch.