The crash happened on the B1261 Main Street at Seamer – near Chew Lane and between the A64 - at around 3.15pm.
Police have confirmed a woman aged in her 60s, driving a light-coloured Kia Picanto, suffered serious injuries while the driver of a blue Citroen C5, a man aged in his 60s, was taken by air ambulance to Hull Royal Infirmary for treatment to abdominal injuries.
The Citroen had been heading south towards Staxton when the head-on crash happened with the Kia, which was travelling in the opposite direction.
The road was closed for several hours as police investigated, re-opening just after 9pm.
Any witnesses, or anyone with information is asked to call North Yorkshire Police on 101 and ask for Neale Rees quoting reference 12170110715.