The two-vehicle collision occurred on the A65, near the Moorgarth Farm Campsite, at about 3.30pm on Wednesday.
Police are now appealing for information.
A North Yorkshire Police spokesperson said: "It involved a light blue Vauxhall Agila and a dark blue Skoda Superb. The Vauxhall was being driven south towards Settle by a woman from the Braford area and her friend, also from the Bradford area. The Skoda was heading in the opposite direction, driven by a man with one female passenger, also from the Bradford area.
"Three people were taken by air ambulance to Preston Hospital and the fourth was taken by road ambulance to Airedale Hospital. The three women suffered serious injuries; the man sustained slight injuries."
Any witnesses to the collision, including those who stopped immediately after the incident to offer assistance, are asked to contact North Yorkshire Police. Call 101, select option one and quote reference 12170108814.