The incident happened around 8:30 p.m. near Weston Road and Starview Lane, near Sheppard Avenue West.
Little information has been released about the circumstances of the crash, but police say one of the two vehicles involved ended up at a home in the area.
According to police, paramedics performed CPR on a patient, but he succumbed to his injuries.
It is unclear if any other injuries have been reported.
Police say drivers should expect extended road closures in the area as officials investigate the incident.