Emergency services were called to the crash on Old Coach Rd, about 20km southeast of Gore at 4.30pm.
A 52-year-old North Island woman, who was a passenger in the campervan, died at the scene.
The campervan driver, a 42-year-old woman also from the North Island, was taken by ambulance to Southland hospital and released on Saturday afternoon.
A 78-year-old Southland man was driving the station wagon and was flown to Dunedin Hospital by helicopter with serious injuries.
Police said the man's injuries were "not thought to be life-threatening" and his condition was stable.
Police would not speculate on the cause of the crash as it remained under investigation. They are seeking information from anyone who saw vehicles on friday evening, or whitnessed the crash.
The road remained closed last night. Diversions were in place as the police serious crash unit investigated the scene.
