A spokesman for the Justice Ministry said the bus crossed into the path of an oncoming truck loaded with bricks in the central state of Guarico, south of Caracas.
"They crashed head on," said Jorge Galindo, the spokesman, in a Twitter message.
Galindo confirmed that 16 people were killed while civil defense officials said 36 others were injured.
"It was a strong impact that ignited a fire in the bus," said Civil Protection director Luis Diaz Curbelo.