A simple mass balance model provides insight into the hydrologic, isotopic, and chemical responses of Lake Titicaca to past climatic changes. Latest Pleistocene climate of the Altiplano is assumed to have been 20% wetter and 5°C colder than today, based on previous modeling. Our simulation of lacustrine change since 15,000 cal yr B.P. is forced by these modeled climate changes. The latest Pleistocene Lake Titicaca was deep, fresh, and overflowing. The latest Pleistocene riverine discharge from the lake was about 8 times greater than the modern average, sufficient to allow the expansion of the great paleolake Tauca on the central Altiplano. The lake δ18O value averaged about −13‰ SMOW (the modern value is about −4.2‰). The early Holocene decrease in precipitation caused Lake Titicaca to fall below its outlet and contributed to a rapid desiccation of paleolake Tauca. Continued evaporation caused the 100-m drop in lake level, but only a slight (1–2‰) increase (relative to modern) in δ18O of early Holocene lake waters. This Holocene lowstand level of nearly 100 m was most likely produced by a precipitation decrease, relative to modern, of about 40%. The lake was saline as recently as 2000 cal yr B.P. The timing of these hydrologic changes is in general agreement with calculated changes of insolation forcing of the South American summer monsoon.