Hato Hone St John says it has treated 20 people after a crash that's killed one and critically injured others near the Devil's Staircase this afternoon.
The crash involved a bus and two cars on State Highway 6 between Queenstown and Kingston.
Police said a person from one of the cars died at the scene and at least two others were reported to have critical injuries.
At least two people from the bus were reported to have serious injuries and a number of other people have moderate injuries, police said.
The crash was reported shortly after 4pm near the intersection with Glen Nevis Station Road at Kingston.
FENZ crews have responded from Kingston, Frankton, Queenstown and Dunedin.
State Highway 6 north of Kingston is closed and is expected to remain closed for several hours.
The NZ Transport Agency said closure points were in place at Kingston township and at Wye Creek.
Motorists were urged to avoid the area as there is no immediate detour available with an alternative route adding two-and-a-half hours to travel time.
The agency says police serious crash investigators will need to check the scene and it's highly likely the road will remain closed until possibly late into this evening.
St John says paramedics and multiple ambulances are at the scene.
Otago Southland Rescue Helicopter has confirmed it was en route to the crash but could not share details about how many helicopters were being sent.
Three fire brigades are responding to the crash which has been labelled heavy rescue on the Fire and Emergency incidents website.
Motorists are urged to delay travel if possible as the road is expected to be closed for some time.
Kingston Corner Shop and Cafe owner Madonna Pradeep said customers have been coming in this evening after being turned back at the road closure.
She was at home when the crash happened, but was called in to help at the store when it got busy.
She said she heard a helicopter overhead, and people were worried.
Customers have been told the road will be closed overnight, as the bus is blocking the road.