A man and a woman also remain in hospital in a critical condition after being rushed to the Royal Victoria Infirmary, in Newcastle.
Shortly before 6.15am on Sunday, emergency services were called to the A1 northbound at Belford to reports of a crash involving a Nissan Note and Toyota Yaris.
The driver of the Nissan Note, a 38-year-old man, sadly died at the scene. His family have been informed and they are being supported by specialist family liaison officers at this time.
A woman, who was in the Toyota Auris, was airlifted to hospital with chest and abdominal injuries where she remains in a critical but stable condition.
A man and two young children, who were also in the Auris, were taken to hospital by road and the man also remains in a critical but stable condition.
The two young children, a boy and a girl, have escaped with minor injuries.
Sergeant Pinner Rana, of Northumbria Police’s motor patrols department, said: “This was a very serious collision which sadly resulted in the death of a man who was involved.
“Our thoughts are with his friends and family at this difficult time, and dedicated family liaison officers are currently offering them support as they come to terms with their loss.
“Four occupants in the Toyota Auris, two adults and two children, have all been taken to hospital and currently are receiving medical attention.
“This was a devastating incident, and the road was subsequently closed for more than eight hours as emergency services attended. We are now committed to finding out the circumstances behind what happened.
“I would like to appeal to anyone who witnessed the collision, or who think they saw any of the cars involved prior to the incident on dashcam footage, to come forward and assist officers with the investigation.”
The two cars collided while travelling in opposite directions on the A1 and the Nissan also collided with an Audi Q5.
Anyone with information is asked to contact 101 quoting reference 826 290919 or Crimestoppers anonymously on 0800 555 111. Alternatively, email