A 467-cm core (B94/3) from the Alta Babicora basin in the Chihuahuan Desert, northern Mexico (29°N, 108°W), documents lake-level and climate changes over the past ca. 65,000 yr. Chronological control is provided by four accelerator mass spectrometry 14C dates and five U-series dates on diatom silica. The core has been analyzed for magnetic susceptibility, loss-on-ignition, carbonate content, sediment chemistry and mineralogy, and pollen and diatom composition. The basin was occupied by a deep freshwater lake throughout the late Pleistocene which, based on shoreline evidence, was at least 19 m deeper than today. The lake shallowed after ca. 57,000 yr B.P. High variability typified the period between 54,600 and 38,000 yr B.P., probably with periodic desiccation and deflation. A deep-water lake was reestablished after 38,000 yr B.P. and persisted until ca. 29,000 yr B.P. Shallowing occurred through the last glacial maximum, although the lake was still deeper than at present. The Pleistocene–Holocene transition was marked by a distinctive change in the diatom flora. There is no diatom record for much of the Holocene, but other proxies indicate generally dry, stable catchment conditions. The Babicora record is more akin to those from the southwest United States than it is to Central America and northern South America. Wet conditions in the late Pleistocene are attributed to winter rainfall from midlatitudes in contrast to the modern, tropical, summer rainfall regime.