Playa-lakes are highly sensitive to hydroclimate changes, which are often reflected in their sediments. In this study, we investigate the paleohydrological evolution of the Fuente de Piedra playa-lake (southern Spain), in connection to climate fluctuations during the Late Pleistocene-Holocene transition. Stable isotopes (delta O-18 and delta H-2) of gypsum hydration water were analyzed to reconstruct the delta O-18 and delta H-2 values of lake water over the past similar to 30,000 years. The highest water delta-values (up to 6.4 parts per thousand for delta O-18 and 24.0 parts per thousand for delta H-2) corresponded to periods when Fuente de Piedra featured as a (semi-)permanent lake (e.g. 22-18.5 cal. kyr BP, 17.4-14.4 cal. kyr BP, 7.0-5.9 cal. kyr BP), coinciding with relatively wetter climate stages in the southern Iberian Peninsula. Conversely, the lowest delta-values (e.g. -1.1 parts per thousand for delta O-18 and -13.0 parts per thousand for delta H-2 between 11.8 and 9.2 cal. ky BP) and periods of no gypsum precipitation (e.g. 12.8-11.8 cal. kyr BP, 5.5 cal. kyr BP-present) are associated with ephemeral lake conditions and more arid climate. This isotope pattern reflects an intensified interaction between the lake and the underlying brackish aquifer during more stable lake stages, driven by wetter climatic conditions. However, during drier phases the lake water was fresher, since reduced aquifer recharge limited the interaction between the brackish groundwater and the lake. Over the long term, the Fuente de Piedra isotope record reveals a sinusoidal pattern that indicates variations in warm-season insolation, confirming orbital control over the hydroclimate of the southern Iberian Peninsula during the Late Pleistocene-Holocene transition.