Police were called to the collision on Wakefield Road close to Nostell Priory shortly after 11.20am.
Numerous road closures surrounding the area are in place, including the A638 Doncaster Road both ways.
Castleford police also said there were closures at the roundabout next to the Ego restaurant on the A638 towards Wakefield up to the next roundabout where the A638 crosses B6428 Cross Hands Lane.
Drivers are urged to avoid the area if possible because it is likely to be very busy.
A West Yorkshire Police spokesperson said: "Officers are at the scene of a serious road traffic collision in Wakefield this afternoon.
"Police were called around 11.23am to Wakefield Road in Ackworth, close to Nostell Priory after two vehicles were in collision and one of the drivers sustained life-threatening injuries.
"Extensive road closures are in place in the area to allow for officers to conduct their enquiries and are expected to remain in place for some time.
"Motorists are advised to find alternative routes and avoid the area where possible."