St John was alerted at 3.31pm and sent two ambulances and the Otago rescue helicopter to the crash scene outside the Alma Caltex petrol station on Oamaru-Alma Road, just south of Oamaru. Police and the Fire Service were also in attendance.
Police confirmed the driver of a car, a 55 year old female, died at the scene.
St John said that another patient, aged in his early teens, is in a very serious condition and was transported to Dunedin Hospital ED by helicopter.
A car and a truck and trailer collided on State Highway 1 about 3.30pm.
Firefighters removed a woman from inside a vehicle. The roof of the vehicle was cut open.
A child was also extracted from the vehicle and is in the care of emergency services.
The St John spokesman said a third person, a male ages aged in his 50s, had suffered minor to moderate injuries and was transported by road to Oamaru Hospital ED for further assessment.
Diversions are currently in place for vehicles.
A police spokesman said details of the crash would be released as they became available.
Anyone who witnessed the crash, or has information, is asked to contact Oamaru Police on (03) 433 1400 or anonymously through Crimestoppers on 0800 555 111.