The driver of a Citroen C2 died at the scene of the incident, which happened at about 18:45 BST on the B4242, north of Abergarwed.
Police closed the road, which leads towards Neath, on Saturday evening as they investigated.
The road has now reopened and an appeal was made for witnesses.
A man has died following a one-vehicle crash in Neath Port Talbot on Saturday.