Ontario Provincial Police (OPP) were called to a two-vehicle collision Thursday evening in Courtright.
Emergency crews responded just before 5 p.m. to Highway 40 between Oil Springs Line and Moore Line.
Lambton OPP said a minivan and passenger vehicle, each carrying one driver and one passenger, collided.
A 51-year-old from London was pronounced deceased at the scene. Three others were taken to hospital with what police described as non-life threatening injuries.
Highway 40 southbound, between Moore and Oil Springs Line, was closed to traffic for several hours, reopening at around 11:30 p.m.
Lambton OPP and the OPP West Region Traffic Incident Management and Enforcement (TIME) Team, continue to investigate the cause of the collision.
Anyone who may have witnessed the crash or have dash cam footage is asked to contact OPP at 1-888-310-1122.
If you wish to remain anonymous, you can contact Crime Stoppers at 1-800-222-8477 (TIPS) or online at www.sarnialambtoncrimestoppers.org.
With files from Mark Brown