The crash happened on the A75 Gretna to Stranraer road at a junction leading to Arnmannoch, Shawhead, at around 3.45pm on Friday.
The vehicles involved were a grey Volkswagen Beetle, a black Vauxhall Corsa and a white Ford Transit van.
Police said that the 79-year-old man driving the Volkswagen Beetle was taken to Dumfries and Galloway Royal Infirmary where he remains in a critical condition.
The 22-year-old woman who was driving the Vauxhall Corsa and a 65-year-old man driving the Ford Transit were taken to hospital for assessment and released.
Sergeant Jonathan Edgar, of Dumfries road policing unit, said: "Given the time of day there would have been a lot of traffic on the road so we're appealing for anyone who saw the collision to contact us.
"Equally we're looking to speak to people who stopped to assist or had dash cameras fitted to their vehicles around the time of the collision."
"If anyone has any information, please contact us on 101 quoting incident number 2443 of 25 October 2019."