And a man was taken by helicopter to hospital in Newcastle with serious injuries.
Police are appealing for witnesses, particularly those with dash-cam footage, who were in the area at around 4.20 pm.
The incident happened near to Nutberry, Annan, when a grey Volkswagen Golf collided with a white Nissan Qashqai.
The driver of the Nissan Qashqai, a 55-year-old woman, was pronounced dead at the scene.
The 52-year-old male driver of the Volkswagen Golf was taken to Royal Victoria Hospital, Newcastle, for treatment.
The road was closed for approximately eight hours for a collision investigation to be conducted at the scene and reopened around 12.20 am on Thursday 6 August.
Anyone with information can contact police on 101 quoting incident number 2196 of 5 August.