The two female Annan Academy pupils were being driven from Annan to Lockerbie Academy in the minibus at about 9.50 am when the crash occurred on the B723 road, about a mile south of Lockerbie.
Emergency services including police, fire and rescue and an air ambulance helicopter attended the scene.
Group manager David Jardine of the Scottish Fire and Rescue Service said: “Appliances from Lockerbie and Annan were mobilised in response to a call from ambulance control and firefighters reached the scene around ten minutes later.
“Two girls were still inside the minibus so extrication plans were quickly developed and put into effect in order to safely release them.”
Working alongside medics, fire and rescue crews used hydraulic cutting equipment and spreaders to free one girl and allow the other to be removed on a rescue board.
The two school pupils sustained leg and back injuries.
One of the girls was flown by air ambulance to the Queen Elizabeth University Hospital in Glasgow while the other girl was taken by road to Dumfries and Galloway Royal Infirmary.
The driver of the car was also taken to hospital and the minibus driver received treatment for minor injuries at the scene of the incident.
The road remained closed as emergency services worked at the scene for more than two hours after the collision.
