The Ene River (Spanish: Río Ene) is a Peruvian river on the eastern slopes of the South American Andes.
The Río Ene is part of the headwaters of the Amazon River whose origin is at the Nevado Mismi south of Cuzco where it first becomes Apurímac River, then the Ene River and Tambo River before its waters meet the Ucayali River which later forms the Amazon.
The Ene is formed at 12°15′45″S 73°58′30″W / 12.2625°S 73.975°W at the confluence of the Mantaro River and the Apurímac River, circa 400 m above sea level, where the three Peruvian Regions Junín, Cusco, and Ayacucho meet.
The river flows in a northwesterly direction at a total length of 180.6 km.
At 11°09′39″S 74°14′48″W / 11.16083°S 74.24667°W Río Ene joins Perené River, at the town of Puerto Prado, 295 m above sea level, and is called the Tambo from then on.