The Chattooga River (also spelled Chatooga, Chatuga, and Chautaga, variant name Guinekelokee River) is the main tributary of the Tugaloo River. Its headwaters are located southwest of Cashiers, North Carolina, and it stretches 57 miles (92 km) or 92 km to where it has its confluence with the Tallulah River within Lake Tugalo, held back by the Tugalo Dam. Both Rivers combine to make the Tugaloo River starting in Lake Yonah. It begins in southern Jackson County, North Carolina, and then it flows southwestward between northwestern Oconee County, South Carolina and eastern Rabun County, Georgia. The "Chattooga" spelling was approved by the USBGN in 1897.

The Chattooga River flows into Tugalo Lake where it joins the Tallulah River. After flowing through Tugalo Dam the combined rivers become the Tugaloo River which, along with the Seneca River, becomes the Savannah River below Lake Hartwell. Downsteam from that point, the water flows into the Atlantic Ocean near Savannah, Georgia.

The river is split into three forks. The Chattooga River is the main fork, running along the state line. The East Fork Chattooga River (sometimes East Prong Chattooga River) runs in from Jackson County, North Carolina and then Oconee County, South Carolina, and is 7 miles (11 km) or 11 km long. The West Fork Chattooga River (variant name Gumekoloke Creek) runs in from Rabun County, Georgia, and is also a variant name for that county's Holcombe Creek, one of its own tributaries.

One of the largest tributaries in the Chattooga basin that flows mainly through private lands is Stekoa Creek. Stekoa Creek flows primarily southeast for approximately 16 miles (26 km) from its headwaters in Mountain City, Georgia, through Clayton, Georgia, to its mouth at the Chattooga River. The Stekoa Creek Basin is approximately 45 square miles (120 km2) in size.

There are also other small tributaries.

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