Our study aims to reconstruct climate changes that occurred at Lake Ohrid (south-western Balkan Peninsula), the oldest extant lake in Europe, between 160 and 70ka (covering part of marine isotope stage 6, MIS 6; all of MIS 5;and the beginning of MIS 4). A multi-method approach, including the “Modern Analog Technique” and the “Weighted Averaging Partial Least-Squares Regression”, is applied to the high-resolution pollen sequence of the DEEP site, collected from the central part of Lake Ohrid, to provide quantitative estimates of climate and bioclimate parameters. This allows us to document climatic change during the key periods of MIS 6 and MIS 5 in southern Europe, a region where accurate climate reconstructions are still lacking for this time interval. Our results for the penultimate glacial show cold and dry conditions, while the onset ofthe “last interglacial” is characterized by wet and warm conditions, with temperatures higher than today (by ca. 2∘C). The Eemian also shows the well-known climatic tri-partition in the Balkans, with an initial pre-temperate phase of abrupt warming(128–121ka), a central temperate phase with decreasing temperatures associated with wet conditions (121–118ka), followed by a post-temperate phase of progressive change towards cold and dry conditions (118–112ka). After the Eemian, an alternation of four warm/wet periods with cold/dryones, likely related to the succession of Greenland stadials and cold events known from the North Atlantic, occurred. The observed pattern is also consistent with hydrological and isotopic data from the central Mediterranean. The Lake Ohrid climate reconstruction shows greater similarity with climate patterns inferred from northern European pollen records than with southern European ones, which is probably due to its intermediate position and the mountainous setting. However, this hypothesis needs further testing as very few climate reconstructions are available for southern Europe for this key time period.