Emergency services were called to Old Coach Rd, in Otaraia, Gore District, about 11am, and two helicopters were sent from Dunedin.
A police spokesman confirmed a second person had sustained serious injuries in the crash, which was close to the intersection with Kaiwera Rd.
A St John spokesman said one person was taken to Dunedin Hospital in a serious condition.
The road was closed for much of the day as the Serious Crash Unit attended the crash site.
The road was eventually reopened about 5pm.
Police have not released the name of the person who died.