The crash occurred at around 8am near the A19 Fulford interchange.
Diversions remain in place.
The man, in his 30s, was driving a black Hyundai i10 which collided with a blue Ford Transit panel van.
The driver of the Transit, a man aged in his early 50s, is receiving treatment for shock.
Motorists are urged to avoid the area until further notice and to follow the diversions that have been put in place.
Anyone who saw the incident, has dash-cam footage or recalls seeing either vehicle prior to the collision, is asked to make contact with the police as soon as possible.
A significant number of vehicles had to take avoiding action but did not stop or contact the emergency services. We need to hear from them too.
Please call North Yorkshire Police on 101, select option 1, and speak to the Force Control Room quoting reference number 12220044588.