Despite the hypothesized importance of the tropics in the global climate system, few tropical paleoclimatic records extend to periods earlier than the last glacial maximum (LGM), about 20,000 years before present. We present a well-dated 170,000-year time series of hydrologic variation from the southern hemisphere tropics of South America that extends from modern times through most of the penultimate glacial period. Alternating mud and salt units in a core from Salar de Uyuni, Bolivia reflect alternations between wet and dry periods. The most striking feature of the sequence is that the duration of paleolakes increased in the late Quaternary. This change may reflect increased precipitation, geomorphic or tectonic processes that affected basin hydrology, or some combination of both. The dominance of salt between 170,000 and 140,000 yr ago indicates that much of the penultimate glacial period was dry, in contrast to wet conditions in the LGM. Our analyses also suggest that the relative influence of insolation forcing on regional moisture budgets may have been stronger during the past 50,000 years than in earlier times.