The 16-year-old was riding a black AJS JSM 60 motorcycle on the A709 near Shillahill Bridge, Lockerbie when he was involved in the collision with a silver Vauxhall Corsa.
It happened at about 11.15 pm and the biker was taken to Dumfries and Galloway Royal Infirmary with serious injuries.
However, the car driver, an 18-year-old man, was not hurt.
Police Constable Mark Walton, of the Road Policing Unit, said: “Enquiries are ongoing to establish the full circumstances and I am appealing to anyone who may have seen the vehicles before the crash to get in touch.
“We are particularly interested in speaking with the driver of a motor car that was in the area at the time of the crash and who overtook the motorcycle shortly before the collision.
“I am also asking anyone who may have dash-cam footage that could assist our enquiries to contact us.”
Anyone who can assist is asked to call Police Scotland on 101, quoting incident number 3931, of Wednesday, 14 September 2022.
