Motorists are urged to avoid the A63 at Barlby while a police investigation is carried out at the scene of the fatal crash.
It occurred at the Sponsored roundabout, which has junctions with the A1 and Magazine Road, at around 4.44pm on Wednesday (June 2).
A small blue car, a small black car and a grey panel van were involved in the crash.
Sadly, the woman driving the blue car died at the scene after receiving CPR from a passing nurse and firefighters using a defibrillator.
The man in the passenger seat of the blue car is receiving treatment at hospital for injuries that are not thought to be serious, police said.
An air ambulance landed at the scene.
North Yorkshire Police said: "This section of the A63 will be closed to traffic until further notice.
"Motorists should avoid the area and follow the diversions put in place by highways.
"A more detailed appeal will be issued in due course, but in the meantime any witnesses are asked to call North Yorkshire Police on 101, select option 1, and speak to the Force Control Room.
"Please quote reference number 12210130779 when providing details. Thank you."