A high-resolution multi-proxy approach, integrating pollen, inorganic and organic geochemical and sedimentological analyses, has been carried out on the Holocene section of the Padul sedimentary record in the southern Iberian Peninsula reconstructing vegetation, environment and climate throughout the last ~ 11.6 cal kyr BP in the western Mediterranean. The study of the entire Holocene allows us to determine the significant climate shift that occurred during the middle-to-late Holocene transition. The highest occurrence of deciduous forest in the Padul area from ~ 9.5 to 7.6 cal kyr BP represents the Holocene humidity optimum probably due to enhanced winter precipitation during a phase of highest seasonal anomaly and maximum summer insolation. Locally, insolation maxima induced high evaporation, counterbalancing the effect of relatively high precipitation, and triggered very low water table in Padul and the deposition of peat sediments. A transitional environmental change towards more regional aridity occurred from ~ 7.6 to 4.7 cal kyr BP and then aridification enhanced in the late Holocene most likely related to decreasing summer insolation. This translated into higher water levels and a sedimentary change at ~ 4.7 cal kyr BP in the Padul wetland, probably related to reduced evaporation during summer in response to decreased in seasonality. Millennial-scale variability is superimposed on the Holocene long-term trends. The Mediterranean forest regional climate proxy studied here shows significant cold-arid events around ~ 9.6, 8.5, 7.5, 6.5 and 5.4 cal kyr BP with cyclical periodicities (~1100 and 2100 yr) during the early and middle Holocene. A change is observed in the periodicity of these cold-arid events towards ~1430 yr in the late Holocene, with forest declines around ~ 4.7–4, 2.7 and 1.3 cal kyr BP. The comparison between the Padul-15-05 data with published North Atlantic and Mediterranean paleoclimate records suggests common triggers for the observed climate variability, with the early and middle Holocene forest declines at least partially controlled by external forcing (i.e. solar activity) and the late Holocene variability associated with internal mechanisms (oceanic-atmospheric). •We carried out a multi-proxy analysis for the last 11.6 cal kyr BP from a new sedimentary record from Padul (Sierra Nevada, Spain).•This record shows a long-term climate pattern mostly forced by insolation, showing a significant climate and environmental shift at 4.7 cal kyr BP.•Millennial-scale climate oscillations are also characterized in this study by the decrease in Mediterranean forest and local response in the lake level, showing possible atmospheric and climate links between the western Mediterranean and North Atlantic areas.