Police have since confirmed a second person had died after the crash.
A third person was flown to Wellington Hospital with serious injuries.
The road was closed for several hours near the spray River Bridge and motorists were advised to avoid the area, as there were no diversions in place.
The serious crash unit had been notified.
Emergency services also responded to a serious single-vehicle crash on Evans St in Timaru.
A police spokesperson confirmed they were called to the scene around 7.45pm.
At 11pm, police confirmed two people had died in the crash.
The crash was first responded to by an off-duty paramedic, according to Fire and Emergency NZ.
Two fire units responded, from Timaru Station and Washdyke, shift manager Simon Lyford said.
Firefighters applied first aid to both patients and were at the crash for roughly an hour.
One fire unit then returned to the scene to help with clean-up after police were finished examining the crash.
Inquiries into the circumstances of the crash are ongoing.