The crash, between a truck hauling whey and a ute, was reported to police at 6.15am.
Senior Sergeant Anthony Bond, of Dunedin, said the 20-year-old driver of the ute crossed the centre line just moments before the crash.
The driver of the milk tanker tried to take evasive action but was unable to avoid the collision, Snr Sgt Bond said.
Police said the driver of the ute, who was from the Clutha area, died at the scene and the serious crash unit was investigating.
A Hato Hone St John spokesman said it sent one helicopter and two ambulances to the incident.
They took one patient with serious injuries to Dunedin hospital, the spokesman said.
Chief Fire Officer Robbie Phillip, of Milton Fire Station, said the station sent a truck and a rescue tender.
Using cutting equipment, they worked with police to help extricate the driver, CFO Phillip said.
The road was closed at Waihola to the north and Milburn to the south, between Limeworks Rd and Phosphate Rd for most of the day.
Police said the road reopened about 6.25pm.
The detour was not suitable for heavy vehicles, Waka Kotahi advised.
