A Fire Service spokesman said an occupant from each 4WD vehicle had to be cut free. Rescue appliances from Willowbank and Lookout Point were called to assist.
Firefighters removed both occupants, who were treated by paramedics, he said.
A St John spokeswoman said both were taken to Dunedin Hospital by ambulance.
A 61-year-old patient suffered a serious head injury and was in a serious condition in the intensive care unit.
The other 19-year-old patient had multiple fractures and was in a serious but stable condition.
Senior Sergeant Dave Scott, of Dunedin, said a diversion was put in place through Leith Valley, but was not suitable for heavy vehicles.
''It was a head-on collision, which indicates one vehicle has crossed the centre line. It has caused quite a bit of disruption for traffic.''
The motorway was closed for several hours last night to allow a crane to removed the vehicles.
