Constable Chris Wakelin, of Balclutha, said a 47-year-old male and a 19-month-old child were also flown to hospital with minor injuries.
All three victims were from Dunedin, Const Wakelin said.
The accident happened about 2.15pm, and early indications were the driver of the van had fallen asleep at the wheel, causing the vehicle to leave the road, Const Wakelin said.
"The vehicle rolled several times, trapping the 16-year-old female in the vehicle."
Fire crews from Clinton and Balclutha had to cut the girl from the wreckage, and the highway was closed temporarily while the Otago Regional Rescue Helicopter landed on the intersection of the highway and Fairview Rd to collect the patients.
During the morning, Lawrence police and fire crews from Lawrence and Milton attended two accidents on State Highway 8.
Senior Constable Robert Wallace, of Lawrence, said the road conditions may have been a factor in a 27-year-old Dunedin man receiving minor injuries after leaving the road at Forsyth Bend, north of Lawrence, about 9.40am.
There was grit on the road, and the car the man was driving had travelled into the water table on the side of the road.
It was unknown if speed was a factor, Snr Const Wallace said.
Emergency services were then called to Evans Flat, on the Beaumont Highway just south of the Tuapeka West Rd intersection, where a Cook Transport stock truck trailer carrying 28 dairy cows had overturned, blocking the road.
The driver, who did not want to be named, said he had been driving for "a long time".
This was the first time he had had an accident, and while he was uninjured, he was "a bit shaken up", he said.
Lawrence Chief Fire Officer Rory Tisdall said 27 cows were herded into a nearby paddock, while one was put down on the side of the road.
The accident is being investigated by the Commercial Vehicle Investigation Unit and Senior Constable Colin Thomas, of Winton, said speed, load and vehicle condition are all being considered as contributing factors.
Traffic was diverted down Franklin Rd for four hours while the trailer was righted and road cleared.
Overall, police throughout New Zealand reported few problems on roads yesterday.
One motorist has been killed on the roads so far this holiday weekend.
A female passenger died after the car she was in crashed near Tokomaru Bay north of Gisborne, just before 6am on Saturday, police said.
