The crash happened on the A684 between Northallerton and the A19 in the area of Winton at about 9.30am today (Friday).
It involved a white Toyota Aygo and a silver / grey Ford Mondeo.
The woman, who was driving the Toyota, was pronounced dead at the scene.
The driver of the Ford was taken to hospital and the extent of his injuries is not yet clear.
North Yorkshire Police are urging anyone who witnessed the collision, saw the vehicles prior to it happening, or has any dashcam footage that could help the investigation, to contact them.