Two small passenger cars collided head on early Friday evening on Highway 25, two miles south of Gordonville, said Cape Girardeau fire battalion chief Steve Niswonger.
Names of the deceased and three victims were unavailable. Cape Girardeau responders assisted Gordonville firefighters at the scene.
One car's engine caught fire and a male occupant suffered burns, Niswonger said.
The second car contained a husband and wife. The wife was killed in the crash. The husband had to be extricated from the vehicle because his right leg was pinned under the dashboard, Niswonger said.
The husband and the two survivors from the first car were flown by air ambulance to local hospitals.