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Palaeoclimate research in subtropical arid Mexico is mainly focused to infer dynamics and geographic distributions of different precipitation regimes, but droughts have received less attention. We present a new sedimentary core record indicating orbital-scale dynamics of droughts that occurred in central-northern Mexico during the late Quaternary. This record is reconstructed from abundances of authigenic carbonate and windblown clastic sediments in a 1026-cm-long sediment core from the Santiaguillo ephemeral lake. The Marine Isotope Stage (MIS) 2 lacked drought, and at least two different droughts were centred at c. 13.5ka and at c. 7ka during the MIS 1. The drought of c. 13.5ka in the Santiaguillo ephemeral lake was contemporary to an interval of droughts in the Basin of Mexico (central Mexico) and stronger aeolian activity in the Baja California peninsula (northwestern Mexico). This synchronous arid condition, observed in the subtropical as well as tropical Mexico, occurred during an interval of higher spring insolation, relatively warmer but fluctuating global temperature, and stronger El Nino-Southern Oscillation. Unsuccessful radiocarbon dating for the lower part of the sediment core led to an assignment of uncertain chronology to droughts that occurred possibly between MIS 5 and MIS 3. Copyright (c) 2017 John Wiley & Sons, Ltd.