During the past 25 ka, southern Ethiopia has undergone tremendous climatic changes, from dry and relatively cold during the Last Glacial Maximum (LGM, 25–18 ka) to the African Humid Period (AHP, 15–5 ka), and back to present-day dry conditions. As a contribution to better understand the effects of climate change on vegetation and lakes, we here present a new Predictive Vegetation Model that is linked with a Lake Balance Model and available vegetation-proxy records from southern Ethiopia including a new phytolith record from the Chew Bahir basin. We constructed a detailed paleo-landcover map of southern Ethiopia during the LGM, AHP (with and without influence of the Congo Air Boundary) and the modern-day potential natural landcover. Compared to today, we observe a 15–20% reduction in moisture availability during the LGM with widespread open landscapes and only few remaining forest refugia. We identify 25–40% increased moisture availability during the AHP with prevailing forests in the mid-altitudes and indications that modern anthropogenic landcover change has affected the water balance. In comparison with existing archaeological records, we find that human occupations tend to correspond with open landscapes during the late Pleistocene and Holocene in southern Ethiopia.