State Highway 65 in the upper South Island is blocked near O'Sullivans Bridge following a crash between two trucks.
Police said one person was reported to have suffered critical injuries in the crash about 7am.
A helicopter was en route to take that person to hospital, and another person with moderate injuries was being taken to hospital by ambulance.
The road, known as the Shenandoah Highway, was expected to remain blocked for some time and traffic was being diverted, police said.
The Transport Agency said the detour would add about 1.5 hours to the journey.