It rises in a confluence of swamps south of Walterboro, flows in a southeast direction and empties into Saint Helena Sound at 32°29′24″N 80°25′26″W / 32.49°N 80.42389°W / 32.49; -80.42389.

Caeser P. Chisolm received a charter to operate ferry service across the Ashepoo River.

[2] During the American Civil War the river was the site of an incursion between Union and Confederate troops.

The 34th Infantry Regiment was ordered to burn a railroad trestle near the river, they boarded the troop steamer Boston but became stranded on an oyster bed.

The men on board were ferried off under fire by Union troops led by George W.