Middlesex OPP say the collision happened at the intersection of Adelaide Street North and Ilderton Road.
They say one person has died from injuries sustained in the collision and two people have been transported to hospital with serious injuries.
The identity of the victim is being withheld by police pending notification of next of kin.
The OPP Traffic Collision Investigation team has been called in to assist with the on-going investigation.
The intersection has been closed to the public and is expected to be closed for the next 7-8 hours as the investigation continues.
Adelaide Street North is closed between 10 and 12 Mile Road while Ilderton Road has been closed between Richmond Street and Highbury Avenue.
Police are asking the public to slow down in the area, take an alternate route and expect delays as the investigation continues.
