It is a tributary of the Altamaha River, which flows to the Atlantic Ocean.
The Ohoopee River rises in Washington County, about 2 miles (3 km) south of Tennille, and flows generally southeastwardly, through or along the boundaries of Johnson, Emanuel, Treutlen, Candler, Toombs and Tattnall Counties.
It joins the Altamaha River 13 miles (21 km) south of Reidsville.
The Ohoopee River is referenced in Larry Jon Wilson's song, "Ohoopee River Bottomland", which appears on Wilson's 1975 album, New Beginnings.
The river valley has recently become the site of a yearly music festival known as "Curly Fest" featuring regional artists.