The T-bone collision at the intersection of Wayne Gretzky Parkway and Lynden Road killed the car's driver, who was pronounced dead at the scene.
Brantford police said the tractor trailer was travelling north on Wayne Gretzky Parkway shortly after noon when it struck the car, which was travelling east on Lynden. The tractor trailer dragged the car into the ditch and rolled over on top of it.
The driver of the truck was taken to a local hospital with non-life threatening injuries.
The tractor trailer had been hauling a tanker of sewage and had to be unloaded before the truck could be righted.
Accident reconstruction experts responded to the scene, as did officials with the ministry of labour.