The westbound bus and a Volkswagon Jetta heading in the opposite direction collided head-on between Innisville, Ont., and Carleton Place, Ont., at about 10:15 a.m. ET Friday, police said. The car then caught fire.
The driver of the car, Damon McCamon, 29, of Lanark County died at the scene.
OPP Const. David Bird said 49 people were on the bus, including the driver.
Police said some passengers on the bus suffered minor injuries and were transported to a community centre in Carleton Place for treatment.
About 30 passengers who had been on the bus boarded a new bus at Carleton Place bound for Toronto.
Jonathon Cole of Toronto said he was sitting in the back seat and held on to a man to prevent him from falling forward. Cole said the bus tire came off in the collision and passengers used it as a step as they exited the bus through the emergency window.
Highway 7 was closed but reopened at 4:45 p.m. ET.
The crash remains under investigation.