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The lake is located at the northern end of the endorheic Altiplano basin high in the Andes on the border of Peru and Bolivia. The western part of the lake lies within the Puno Region of Peru, and the eastern side is located in the Bolivian La Paz Department.

The lake consists of two nearly separate subbasins connected by the Strait of Tiquina, which is 800 m (2,620 ft) across at the narrowest point. The larger subbasin, Lago Grande (also called Lago Chucuito), has a mean depth of 135 m (443 ft) and a maximum depth of 284 m (932 ft). The smaller subbasin, Wiñaymarka (also called Lago Pequeño, "little lake"), has an average depth of 9 m (30 ft) and a maximum depth of 40 m (131 ft). The overall average depth of the lake is 107 m (351 ft).

Five major river systems feed into Lake Titicaca. In order of their relative flow volumes these are Ramis, Coata, Ilave, Huancané, and Suchez. More than 20 other smaller streams empty into Titicaca. The lake has 41 islands, some of which are densely populated.