Emergency services were called to the crash on the Tarras-Cromwell Rd on State Highway 8 in Bendigo, north of Cromwell, shortly after 3pm.
Detective Sergeant Brian Cameron confirmed that one person had died.
That person had been trapped in the vehicle. Five others were able to get out.
Two passengers would likely be taken to Dunedin Hospital via Otago Regional Rescue Helicopter.
The other three would be treated nearby for minor injuries.
The New Zealand Transport Agency advised that the road was closed between the Bendigo loop road and Northburn Station Rd.
It advised northbound traffic to use SH8B, SH6 and SH8A, and the reverse for southbound vehicles.
Police said the road was expected to be closed for several hours and diversions were in place at Dead Man's Pt and Bells Rd.
