Constable Chris Wakelin, of Balclutha, said the truck and trailer unit was fully loaded, carrying about 600 sheep to slaughter in Invercargill, when the trailer tipped about 9.40am.
The driver was not hurt.
The sheep were eventually led into a local farmer's paddock, Const Wakelin said. There was minor disruption to motorists.
W. E. Perrin Ltd truck driver Garth McLachlan was one of the first to attend the accident.
"The trailer was on its side ...and there were lambs everywhere," he said.
"We took care of all the live [sheep], then we assisted with the clean-up."
Const Wakelin said about 100 sheep were injured. Some were humanely destroyed on the side of the road.
The trailer was eventually pulled back on to its wheels by a 20-tonne tractor excavator.
Police also had to contact the Clutha District Council to notify it of damage to the road, and so it could advise motorists travelling on the Papatowai Highway to take extra care.
Investigations into the cause of the accident were continuing.