The collision between a Ford Ka and a Ford Focus happened on the A1 near Torness power station in Dunbar, East Lothian, at about 7.40pm yesterday.
A 21-year-old female passenger in the Ka suffered serious injuries and died at the scene.
The 21-year-old woman driving the Ka and another female passenger, aged 20, were also injured, as were the 23-year-old man driving the Focus and his 20-year-old female passenger.
Three of those involved were airlifted to Edinburgh Royal Infirmary by a search and rescue helicopter from RAF Boulmer, near Alnwick in Northumberland.
The other casualty was taken by ambulance to the same hospital.
The road was closed for about six hours while police carried out investigations.
Police Scotland appealed for anyone with information to contact them.