Police say the man was travelling southbound along the stretch of road at Hurst Green when he had a suspected heart attack at the wheel of his car just before 12.45pm.
The man’s silver Hyundai left the road and collided with a tree.
Members of the public and a passing Kent paramedic battled to save the motorist, but he was pronounced dead at the scene.
The man has not yet been identified, but he is believed to be aged in his 70s and from the Hastings area.
Police say there were no passengers in the vehicle at the time of the accident.
Police closed the A21 between Station Road and the junction with Merriments Lane and traffic was diverted.