Police said the crash occurred about 4pm when the driver of a southbound car, which was towing a trailer carrying a racing car, lost control and crossed the centre line, colliding with a northbound vehicle.
Senior Constable Darren Cox, of Balclutha police, said the 43-year-old female driver of the southbound car, and the 59-year-old male driver of the northbound car, were trapped in their vehicles for about 20 minutes.
They suffered moderate to serious injuries and were airlifted to Dunedin Hospital.
A 47-year-old male passenger in the southbound car suffered moderate shoulder injuries and was also transported to hospital.
The southbound car was towing a Suzuki Swift racing car, the windows of which were marked with the driver's name, Cox (not believed to be related to the constable).
There is a race meeting of the Suzuki Swift Cup at Teretonga, in Invercargill, tonight.
The road was closed for about two hours, and a diversion was in place for light traffic over Phosphate Rd, Snr Const Cox said.
Inquiries are continuing.
