This paper explores the impact of environmental, e.g. sea level rise, and climatic events, e.g. abrupt cooling events, on Mesolithic populations (ca. 11,350 to 6600 cal BP) living in the western Scheldt basin of Belgium and Northern France. The Mesolithic in this study-area has been extensively studied during the last few decades, leading to an extensive database of radiocarbon dates (n = 418), sites (n = 157) and excavated loci (n = 145). A multi-proxy analysis of this database reveals important changes both chronologically and geographically, which are interpreted in terms of population dynamics and changing mobility and land-use. The results suggest a population peak and high residential mobility in the Early Mesolithic, followed by a population shift and increased intra-basin mobility in the Middle Mesolithic, possibly triggered by the rapid inundation of the North Sea basin. The situation during the Late Mesolithic remains less clear but a possible reduction in the mobility seems likely. Currently there is little evidence supporting a causal link between these diachronic changes in human behavior and the 9.3 and 8.2 ka cooling events. Most of the observed changes seem more in response to long-term climatic and environmental changes during the Early and Middle Holocene, hinting at considerable resilience.