It happened on the B729 Dumfries to Carsphairn road near Dunscore around 10.20 am and involved a white Nissan Navara pick-up which collided with a wall by the road.
The 42-year-old man driving the vehicle was subsequently airlifted to the Queen Elizabeth University Hospital in Glasgow for treatment to serious injuries.
He was the sole occupant of the vehicle and no other vehicles were involved.
Police are appealing for information and Sergeant Leigh McCulloch, of Dumfries and Galloway Road Policing, said: “Enquiries are ongoing to establish the full circumstances which led to this crash and I would ask anyone who may be able to help to come forward.
“Anyone who was on the road around the time of the crash or who may have dashcam footage is urged to get in touch with us as soon as they can.”
Anyone with information can contact police on 101, quoting incident 0903 of 25 May.