The Mema is a semi-arid region in central Mali with a rich archaeological heritage indicating the former existence of large urban settlements. The archaeological data suggest millennia of occupation history of the Méma preceding relatively sudden abandonment by the 14th or 15th century AD. Population numbers have remained low since then and today’s human presence in the area is sparse and largely mobile. Geomorphologically, the Méma can be characterized as a graben hosting various generations of aeolian landforms and (presently mostly dry) interdunal channels and lakes, linked to the neighbouring Inland Niger Delta floodplain. Given this setting, and the variability of the Sahelian climate, climatic contributions to the region’s sudden abandonment are likely. A geomorphological survey of the region, and interpretation of the observed geomorphological record in terms of climatic history, aimed at providing a basis for understanding the intensive occupation and subsequent abandonment of the Méma. The results of this study underscore dramatic Holocene climatic variability, leading to the region’s present geomorphological diversity, but also suggest that neotectonic movements constitute an important additional cause of regional desiccation. Both may have encouraged prehistoric people to abandon the Méma after a long period of occupation.