This paper develops a regional dataset of change at 381 settlements for Lycia-Pamphylia in southwest Anatolia (Turkey) from volume 8 of the Tabula Imperii Byzantini–a compilation of historical toponyms and archaeological evidence. This region is rich in archaeological remains and high-quality paleo-climatic and -environmental archives. Our archaeological synthesis enables direct comparison of these datasets to discuss current hypotheses of climate impacts on historical societies. A Roman Climatic Optimum, characterized by warmer and wetter conditions, facilitating Roman expansion in the 1st-2nd centuries CE cannot be supported here, as Early Byzantine settlement did not benefit from enhanced precipitation in the 4th-6th centuries CE as often supposed. However, widespread settlement decline in a period with challenging archaeological chronologies (c. 550–650 CE) was likely caused by a “perfect storm” of environmental, climatic, seismic, pathogenic and socio-economic factors, though a shift to drier conditions from c. 460 CE appears to have preceded other factors by at least a century.