The 66-year-old suffered spinal and chest injuries after her white Toyota Yaris was in collision with a white Daf recovery lorry and a grey BMW.
She was initially taken to Dumfries and Galloway Royal Infirmary, before being transferred to the Queen Elizabeth University Hospital in Glasgow.
The drivers of the other two vehicles were uninjured.
The collision happened at 9.10 am between the A701 and A709 roundabouts.
Emergency services rushed to the scene and the road was closed for over six hours for a crash scene investigation.
Police are appealing for witnesses and PC Paul Watson said: “We would like to hear from any witnesses who were on the A75 at the scene when the collision happened.
“We know that the road was busy at the time and anyone with any information which might help should call us at Dumfries on 101.”