The Keiskamma River (Afrikaans: Keiskammarivier) is a river in the Eastern Cape Province in South Africa. The river flows into the Indian Ocean in the Keiskamma Estuary, located by Hamburg Nature Reserve, near Hamburg, 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. The Keiskamma River marked the border between the Cape Province and former British Kaffraria, known also then as Queen Adelaide's Province, until 1847.