He was taken to Dumfries and Galloway Royal Infirmary after the crash near Steven’s Croft at about 11 pm.
Police Scotland are appealing for witnesses to contact them as they try to piece together the incident.
The vehicle, a BMW X5 series, was travelling south with four occupants when it left the carriageway, mounted the embankment and rolled onto the adjacent B7076.
Medical staff have said the 31-year-old is in a critical condition, but the three other passengers sustained only minor injuries.
Sergeant Leigh McCulloch, from the Trunk Road Policing Group based at Lockerbie, said: “This was a serious road crash which has left one occupant of the vehicle seriously injured.
“Lane one of the A74 (M) southbound was closed. A stretch of the B7076 was closed whilst specialist officers conducted enquiries following the initial emergency response.
“Enquiries are ongoing to determine the circumstances surrounding the crash.
“If anyone has any information that can help with our investigation, I ask that they contact road policing officers at Lockerbie.”
Information can be passed to officers at the Trunk Road Policing Group via the 101 number.