Officers were called to Wakefield Road, close to Nostell Priory, at 11.23am on Saturday.
A blue Peugeot 206 and grey Ford Kuga collided, police said.
The driver of the Peugeot, a 26-year-old man, was fatally injured and died at the scene. His family have been informed.
The driver of the Ford, a 59-year-old woman, suffered minor injuries.
Road closures have been in place to allow officers to continue their investigation.
Detective Constable Deborah Farley, who is leading the investigation with the Major Collision Enquiry Team, said: “This incident has taken place on one of the main routes in to Wakefield and I would appeal to anyone who has been in the area and seen either vehicle prior to the incident, or witnessed the collision itself to come forward with any information.”
Anyone who has any information or witnessed what took place is asked to contact the Major Collision Enquiry Team via 101, quoting log 846 of December 23.