Around 4.2 ka BP, several ancient civilizations declined, during a climatic fluctuation documented by many archaeological and palaeoenvironmental studies of locations around the world. However, the nature, timing, and regional expressions of this climate event are still uncertain. Through a detailed survey of Mediterranean pollen records, we show clear spatiotemporal patterns in tree cover variations over the Mediterranean Basin, characterized by regions with increasing forest cover before 4.2 ka BP and decreasing afterwards (NW Iberian Peninsula, South-central Mediterranean), and regions with contemporary opposite dynamics (Mediterranean Iberian Peninsula, Morocco, S Balkan Peninsula, and the Levant). At the same time, in the geographical belt longitudinally stretching from southern France to the Caucasus, no significant changes in tree cover are recorded. This coherent system of ecological configurations, possibly determined by the reorganization of semi-permanent high/low pressure cells, brings order to the contradictory climate signals of the 4.2 ka BP event. The discovery of ecological processes of opposite polarity at a sub-continental scale sheds new light on geographical patterns of past and present environmental vulnerability to rapid climate change in the Mediterranean Basin.