Police were called to reports of a serious road traffic collision at about 7.20pm on the A3102 Sandridge Hill at the junction with Brick Hill.
Officers said that a Land Rover Defender 90 was in collision with a Volkswagen Passat.
A spokesman said: “A teenage girl sustained what are thought to be life-changing injuries and was transported to hospital by Wiltshire Air Ambulance.
“A man was also taken to hospital to be treated for minor injuries sustained in the collision.”
Police closed the road in both directions between Eastern Way and the A342 following the crash.