Significance The Terminal Classic decline of the Maya civilization represents a key example of ancient societal collapse that may have been caused by climate change, but there are inconsistencies between paleoclimate and archaeological evidence regarding the spatial distribution of droughts and sociopolitical disintegration. We conducted a new analysis of regional drought intensity that shows drought was most severe in the region with the strongest societal collapse. We also found that an earlier drought interval coincided with agricultural intensification, suggesting that the ancient Maya adapted to previous episodes of climate drying, but could not cope with the more extreme droughts of the Terminal Classic. Paleoclimate records indicate a series of severe droughts was associated with societal collapse of the Classic Maya during the Terminal Classic period (∼800–950 C.E.). Evidence for drought largely derives from the drier, less populated northern Maya Lowlands but does not explain more pronounced and earlier societal disruption in the relatively humid southern Maya Lowlands. Here we apply hydrogen and carbon isotope compositions of plant wax lipids in two lake sediment cores to assess changes in water availability and land use in both the northern and southern Maya lowlands. We show that relatively more intense drying occurred in the southern lowlands than in the northern lowlands during the Terminal Classic period, consistent with earlier and more persistent societal decline in the south. Our results also indicate a period of substantial drying in the southern Maya Lowlands from ∼200 C.E. to 500 C.E., during the Terminal Preclassic and Early Classic periods. Plant wax carbon isotope records indicate a decline in C ₄ plants in both lake catchments during the Early Classic period, interpreted to reflect a shift from extensive agriculture to intensive, water-conservative maize cultivation that was motivated by a drying climate. Our results imply that agricultural adaptations developed in response to earlier droughts were initially successful, but failed under the more severe droughts of the Terminal Classic period.