The river flows into the Indian Ocean in the Keiskamma Estuary, located by Hamburg Nature Reserve, near Hamburg,[1] midway between East London and Port Alfred.

The Keiskamma flows first in a southwestern and then in a southeastern direction after meeting its main tributary, the Tyhume River.

[3] Presently this river is part of the Mzimvubu to Keiskamma Water Management Area.

[4] There is a small population of the endangered Eastern Province rocky (Sandelia bainsii) in the Tyhume River, part of the Keiskamma river basin.

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