A police media spokeswoman said emergency services, including St John ambulance and volunteer firefighters, were called to a crash near Devil’s Staircase at 1.37pm.Two ambulances and a helicopter were called to the scene.
St John communications adviser Chrissy Hamilton said one person was flown to Dunedin Hospital with "serious injuries" and two other patients were taken to Lakes District Hospital by ambulance with minor injuries.
One of the cars appeared to have hit a rock wall and was badly damaged.
The other car was up against a barrier on the lake side of the highway.
Traffic was stopped in both directions, causing large queues on each side of the highway, before it started flowing as normal shortly after 3pm.