Fifty-year-old Robert Sharp, from Wyndford Road in Maryhill, Glasgow, was travelling in a grey Peugeot 307 and was seriously injured along with the car driver in the smash which happened near Kirtlebridge just after 4 pm.
Mr Sharp was treated at the scene by doctors and paramedics before being airlifted to the city’s Queen Elizabeth University Hospital, where he died overnight.
The collision happened on the A74M, about three miles south of junction 20 for Eaglesfield, and also involved a white Scania articulated lorry being driven by a 59-year-old man from Reading. He was not injured.
However, the car driver, a 39-year-old man from Callander, was taken to the Cumberland Infirmary at Carlisle for treatment. He is believed to be still in hospital.
Police and firefighters from Annan and Gretna rushed to the scene to release the two men from the car.
The southbound carriageway was closed for six hours as work went on at the scene and also for a full crash scene investigation.
Meanwhile, police also temporarily closed the northbound carriageway to allow the air ambulance helicopter to land and then take-off.
Appealing for witnesses to the crash, Sergeant Leigh McCulloch of the Trunk Roads Policing Group at Lockerbie said: “We want to hear from anyone who may have been on the A74(M) around this time near the locus and who may have witnessed the crash.”
He added: “Anyone who has any information which they would want to pass on can call the Trunk Roads Policing Group at Lockerbie on the 101 number.”