The crash occurred on Highway 40, near Heritage Line, near Wallaceburg, Ont., at about 4 p.m. Saturday.
The Ontario Provincial Police say a Toyota crossed into the path of an oncoming Chrysler.
The man driving the Toyota died. Police have identified the deceased as 53-year-old Antony Nascimento of Toronto.
A 51-year-old woman, Rooshmanie Rambarran, also of Toronto, was a passenger in the vehicle and survived the crash. Police say she is being treated for non-life threatening injuries in hospital.
Catherine Caron, a 19-year-old woman from Wallaceburg, Ont., was the driver of the Chrysler. She is also being treated for non-life threatening injuries.
Police say the collision remains under investigation but charges are not expected.