The collision between a sedan carrying five people and a courier van with one occupant, happened at the intersection of State Highway's 8B and 6, near Nichol's Garden Centre.
Constable Dean Schroder said it appeared the driver of the sedan failed to give way as he was turning right on to SH6, in the direction of Wanaka.
The vehicles collided and the male driver of the sedan, believed to be a 29-year-old Taiwanese man who was working in the area, died at the scene.
His male front seat passenger was taken by ambulance to Dunstan Hospital with serious injuries and later airlifted to Dunedin Hospital.
Three females in the back seat had to be cut from the car, and were flown by two rescue helicopters to Dunedin Hospital with serious injuries.
One of the back seat passengers died in Dunedin Hospital overnight, and the other two remain in a critical condition.
The female driver of the courier van received minor injuries and was treated at the scene.
More than 15 emergency service staff attended the accident.
Const Schroder said conditions at the time of the crash were dry and clear. A police investigation had started.
Detours were in place while the intersection was closed for about two and a-half-hours.
