The reserve is located in the provinces of Sucumbíos and Orellana at the northern part of the Ecuadorian Amazon basin. Created in 1979, the reserve spans an area of 590,112 ha (1,458,198 acres) with altitudes ranging from 177 to 326 m.a.s.l.
It is named after the Cuyabeno River which overflows during its course creating a group of 14 lagoons and it is the largest wetland area in the Ecuadorian Amazon region.
It has been historically protected by the indigenous ethnic inhabitants of the reserve: Siona, Secoya, Cofan, Kichwa and Shuar nationalities. Cuyabeno is home to a wide variety of unique flora and fauna in the world.