It happened just before 1.55pm on the A19 at Escrick, between York and Selby.
A black Audi and a black Kia crashed head-on leaving a woman dead and several people seriously injured.
The road was closed on Tuesday for a number of hours as officers investigated and cleared the scene.
North Yorkshire Police are now appealing for witnesses who saw either vehicle before the crash or who witnessed the collision to contact them.
They are especially keen to hear from anyone who has dashcam footage.
Anyone who can help the investigation is asked to call North Yorkshire Police on 101, quoting reference 12190238470.