The source of the river is formed from the confluences of its upper tributaries, the Tariku and Taritatu Rivers. From there it flows northwards in a great valley through the Van Rees Range (Pegunungan Van Rees), to reach the lowland marshes of its broad river delta. The Mamberamo discharges into the Pacific Ocean at the northern point of Point D'Urville (Tanjung D'Urville).