An 18-year-old woman was driving a Toyota Yaris when it was in a crash with a Ford Transit van on the A595 near Bootle at 19:55 BST on Friday.
She and her front seat passenger, also 18, were pronounced dead at the scene.
A third 18-year-old woman, in the back of the car, was flown by air ambulance to hospital where her condition is said to be "critical".
The 51-year-old man driving the van was also flown to hospital, where he is in a serious but stable condition.
The road was closed for six hours for the vehicles to be examined and then removed, Cumbria Police said.
The force is appealing for witnesses.
Two teenagers have been killed and another seriously injured in a car crash in Cumbria.