Emergency services were called at around 6am today (Thursday) to the collision in York Road, Doncaster.
Police said a white Audi RS4 and a black Ford Mondeo were involved in the collision.
One man has died and his family has been informed, and are receiving support.
The other driver has been taken to hospital with serious injuries.
The road was closed for a time while emergency services responded but it is now open.
Enquiries are ongoing and witnesses are asked to call 101 quoting incident number 114 of 2 March 2017.