A white Audi RS4 and a black Ford Mondeo were involved in the smash on York Road at 6am today.
Firefighters called to the crash scene said one casualty had to be cut free from the wreckage of one of the cars.
A South Yorkshire Police spokeswoman said: "Police and emergency services were called at around 6am this morning to reports of a serious collision in York Road, Doncaster.
"It is reported that a white Audi RS4 and a black Ford Mondeo were involved in the collision.
"One man is understood to have died as a result of the collision. 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 re-open."
Witnesses should call South Yorkshire Police on 101.