Emergency crews were called to Kingston Road just after 3 a.m. to a two-vehicle crash.
Toronto police said a 31-year-old man was driving a Toyota westbound on Kingson. At the same time, a 23-year-old man was driving a Honda eastbound on the same street.
For an unknown reason, the Toyota crossed over the centre line and crashed into the Honda.
Two people in each car were taken to hospital including one passenger, a 29-year-old man who had been in the Toyota. Police said that man suffered life-threatening injuries.
All other injuries are considered non-life threatening.
The driver of the Toyota was arrested for impaired driving.
Police continue to investigate.