Holocene centennial-scale paleoenvironmental variability has been described in a multiproxy analysis (i.e., lithology, geochemistry, macrofossil, and microfossil analyses) of a paleoecological record from the Padul Basin in Sierra Nevada, southern Iberian Peninsula. This sequence covers a relevant time interval hitherto unreported in the studies of the Padul sedimentary sequence. The  ∼  4700-year record has preserved proxies of climate variability, with vegetation, lake levels, and sedimentological change during the Holocene in one of the most unique and southernmost wetlands in Europe. The progressive middle and late Holocene trend toward arid conditions identified by numerous authors in the western Mediterranean region, mostly related to a decrease in summer insolation, is also documented in this record; here it is also superimposed by centennial-scale variability in humidity. In turn, this record shows centennial-scale climate oscillations in temperature that correlate with well-known climatic events during the late Holocene in the western Mediterranean region, synchronous with variability in solar and atmospheric dynamics. The multiproxy Padul record first shows a transition from a relatively humid middle Holocene in the western Mediterranean region to more aridity from  ∼  4700 to  ∼  2800 cal yr BP. A relatively warm and humid period occurred between  ∼  2600 and  ∼  1600 cal yr BP, coinciding with persistent negative North Atlantic Oscillation (NAO) conditions and the historic Iberian–Roman Humid Period. Enhanced arid conditions, co-occurring with overall positive NAO conditions and increasing solar activity, are observed between  ∼  1550 and  ∼  450 cal yr BP (∼  400 to  ∼  1400 CE) and colder and warmer conditions occurred during the Dark Ages and Medieval Climate Anomaly (MCA), respectively. Slightly wetter conditions took place during the end of the MCA and the first part of the Little Ice Age, which could be related to a change towards negative NAO conditions and minima in solar activity. Time series analysis performed from local (Botryococcus and total organic carbon) and regional (Mediterranean forest) signals helped us determining the relationship between southern Iberian climate evolution, atmospheric and oceanic dynamics, and solar activity. Our multiproxy record shows little evidence of human impact in the area until  ∼  1550 cal yr BP, when evidence of agriculture and livestock grazing occurs. Therefore, climate is the main forcing mechanism controlling environmental change in the area until relatively recently.