The 83-year-old man was the driver of a Honda Jazz, which was in collision with another car on the A75 at its junction with the B6357, at the east junction for Annan.
He was cut free from his car and taken to Dumfries Infirmary, where he died earlier today.
The smash happened at about 11 am on Sunday and the 69-year-old female driver of the other car, an Audi A1, was also taken to hospital, along with the passengers of both vehicles.
Police are appealing for witnesses and Sergeant Leigh McCulloch, of the Road Policing Unit, said: “We are carrying out a full crash investigation into this collision and would ask that anyone who may have witnessed it to get in touch with us at Lockerbie on the 101 number.”