A helicopter has been dispatched to the scene and will take the seriously injured patient to Dunedin Hospital, the St John spokeswoman said. The other two will be taken to hospital by ambulance.
Nobody was trapped in the vehicle, the Fenz spokesman said.
State Highway 1 is currently closed while emergency services remain working at the scene.
Nine people have died on the roads around the country since Christmas Day, more than doubling last year's entire road toll.
Terry Charleston, 34, and Rebecca McAlees, 24, died in a crash on Christmas night on Clevedon-Kawakawa Rd, south of Auckland.
Hours later, two young men - mates Jack Heritage Jnr and Viliami Muru-Teutau, both 20 years old, died in the early hours of Boxing Day after the vehicle they were in crashed on Triangle Rd in Massey, West Auckland.
James and Kareen Malcolm, of Invercargill, were killed on Monday when their motorcycle collided with a milk tanker on the Riverton-Wallacetown Highway (State Highway 99), between Taramoa Rd and Price Rd.
The eighth fatality was at Kahikatea Rd, Dairy Flat, on Tuesday.
And last night, one person died after a crash on Russley Rd in Christchurch near the city's airport.