Late night crash closes road in both directions
One man was arrested on suspicion of drug driving and causing serious injury by careless driving and the other on suspicion of causing serious injury by dangerous driving.
Both remained in police custody.
Det Sgt Shona Birkby described the crash as "incredibly serious".
"We are keen to identify the driver of an HGV van which is believed to have been travelling along the A5 at the time of the incident and may have witnessed the collision, as well as a number of witnesses who left the scene prior to police arrival," she added.
Anyone with information was urged to contact the police.