Police shut the B1248 road near North Grimston in the Malton area for two hours while they investigated the scene of the collision between a black Vauxhall Astra and a blue Honda Jazz.
The injured woman, who was inside the Honda, was taken to York District Hospital by ambulance where police said she remains in a serious but stable condition.
The Honda was being driven by a 60-year-old woman towards Malton and the Vauxhall by a 29-year-old man in the direction of Hull when the collision happened at around 5.30pm on Saturday (July 28).
Anyone who saw the collision or who recalls seeing either of the vehicles before hand is asked to contact North Yorkshire Police on 101, quoting reference number 12180138450.
Police said they would particularly like to speak to the occupants of two vehicles that were travelling in front of the Vauxhall prior to the collision, which were also being driven towards Hull.