Police say the accident happened around 5.10 pm on Saturday evening when a Suzuki Grand Vitara travelling east and a west-bound Vauxhall Meriva collided on the A75, Gretna to Stranraer road, near to Ardachie, Kirkcowan.
The 36-year-old driver of the Suzuki Grand Vitara, Paul McCleary of Race Green Avenue, Newton Stewart died at the scene.
And Elizabeth Walton, aged 77, of McDowall Drive, Stranraer, a passenger in the Vauxhall Meriva, was taken by ambulance to Dumfries and Galloway Royal Infirmary where she died a short time later.
Four people, two men, aged 81 and 72, and a woman aged 70, from the Vauxhall Meriva and a 33-year-old woman from the Suzuki Grand Vitara were injured in the crash.
The 81-year-old driver was taken by helicopter to the Queen Elizabeth University Hospital in Glasgow where he was detained in a ‘serious’ condition.
Meanwhile, the 70-year-old woman remains at Dumfries Infirmary and the 72-year-old man is receiving treatment at Stranraer Community Hospital. Both are in a ‘stable’ condition.
The woman, who was 33 and sustained minor injuries, was released after overnight treatment at Dumfries Infirmary.
A Police Scotland spokeswoman said “Enquiries into the crash are continuing. Any witnesses are asked to contact Dumfries Road Policing Unit via 101 quoting incident number 2987/06.”
A report is being prepared for the Procurator Fiscal.