Emergency services attended the Berwyn area shortly after 11:40am following a report of a three-vehicle collision which involved a black Kawasaki ZZR motorcycle, a Swiss registered campervan and a red heavy goods vehicle.
The motorcyclist was subsequently taken to hospital with serious injuries.
The road remains closed whilst investigations are ongoing.
Sergeant Alun Jones of the Roads Crime Unit said: “I am urging anybody who witnessed the collision or was travelling along the A5 near to Berwyn prior to 11.40am and has dashcam footage to contact us.”
“Additionally, anyone who has footage of the motorcyclist, who was travelling southbound in company with another three motorcycles, or the HGV or campervan to contact us.”
Anybody with information that could assist our investigations should contact us via our website or by calling 101, quoting reference number C115191.