Data are presented from four new cores from the Pátzcuaro basin in the volcanic highlands of central Mexico, which provide new insights into climate change and human impact over the last 23,000 cal. yr (19,000 14C yr) BP. The cores have been analysed for a range of proxies including mineral magnetic properties, loss-on-ignition, diatoms and stable isotope composition (δ18O and δ13C). High lake levels are recorded in the late Pleistocene and early Holocene, with a probable shift from winter precipitation from the Pacific in the late Pleistocene, to the modern summer regime in the early Holocene. Gradual drying and increased climatic variability are indicated from the early Holocene, but particularly since 4000 cal. BP, consistent with southward displacement of the ITCZ. The changing chemical composition and depth of the lake led to the accumulation of ostracod layers. The timing of the late Holocene dry intervals corresponds to global periods of rapid change driven by Bond and/or solar cycles. By combining a range of proxies we have been able to identify climatic change, even within a period of significant human disturbance. The use of multiple cores indicates that a coherent climatic signal is recorded even in a basin subject to tectonic disturbance. This study also provides new data to support the interpretation of major human impact on the basin in both the pre- and post-Hispanic periods, refuting continued suggestions that basin-wide erosion occurred only after the Spanish conquest. A new model of sediment un-mixing has been applied to identify different source materials contributing to deposition.