Police were called to a crash involving two heavy goods vehicles and a red Toyota Yaris between Watchfield and Faringdon at just past 12.50am this morning (January 9).
Police said tragically, the male driver of the Toyota Yaris, aged in his 70s, died of his injuries at the scene.
The two lorry drivers were taken to hospital for treatment, but their injuries are not believed to be serious.
READ MORE: Live – A420 closed following serious crash
One of the lorries jack-knifed and collided with a stationary lorry in the initial collision.
Investigating officer Sergeant Tony Jenkins, of the Roads Policing Unit, said: “First and foremost, our thoughts are with the family of the man who has tragically died in this collision.
“They are being supported by specially trained family liaison officers.”
Police are appealing for witnesses and dash-cam footage.
Sgt Jenkins said: “I am appealing to anybody who was driving in the area at the time of the collision and has any information that can assist this investigation to please get in touch with us.
“If you have dash-cam in your vehicles, I would ask you to please check this and contact us to provide this to us.”
Anyone with information can make a report online or by calling 101, quoting reference 43240011641.
The A420 has been closed for several hours while the vehicles were recovered and an investigation was under way.
It currently remains closed for resurfacing work and is expected to re-open later this evening.
Police asked drivers to avoid the area and find alternative routes.