A St John spokeswoman said a first response unit, a prime doctor, two helicopters, and an ambulance went to the scene and treated three patients.
Two were airlifted to Dunedin Hospital, one in a serious condition, and the other in a critical condition.
The third person had minor injuries and was taken to Dunedin Hospital by ambulance, she said.
An Otago Daily Times reporter at the scene said in an unrelated incident a man who was photographing the helicopters responding to the crash received a head injury after he was caught in the down-draft of a helicopter taking off.
The man fell and struck his head on a steel beam, but did not appear to require medical attention.
A Fire and Emergency New Zealand spokesman said crews from Alexandra, Naseby and Ranfurly attended the scene and helped extract people from both vehicles.
The crash happened outside Gilchrist's Store.
Shop assistant Rochelle Drury said she had heard a Mini travelling up and down the road at speed.
"I heard it go past once, then twice, then I heard the crash."
"I thought 'Christ, the road toll [for Anzac weekend] is going to go from 11 to 12 now'."
Oturehua Railway Hotel publican Grahame Jones said that the Minis had been speeding in the town's main street but he did not see the crash.
"I saw them before [the crash] being silly, racing up the street while others were out there taking photos."
Due to the popularity of the Otago Central Rail Trail, he had been campaigning for the speed limit to be reduced from the current 70kmh, he said.
Another nearby resident also heard speeding cars, then a big bang, followed by a woman screaming.
Alexandra road policing Sergeant Bruce Martin said crash investigations were ongoing.
He would not speculate on whether speed was a factor.
Members of Mainland Mini Meander declined several requests for comment, saying the incident was under police investigation.