Officers were called to the 2100 block of Cheek Road at 2:18 p.m. on Tuesday.
Durham police said the victim was driving on Cheek Road when the occupants in another car fired a shot at the victim's car.
The victim suffered a gunshot wound and then crashed into the back of a tractor-trailer parked on the side of the road.
He was then taken to the hospital with serious injuries.
The shooting remains under investigation.