This paper examines the evidence for climatic changes in the Eastern Mediterranean for the period 200–800 AD and offers hypotheses on the role of climatic fluctuations in the societal developments that occurred in this region at the end of Antiquity. The geographical focus of the paper includes Anatolia and the Levant, two major regions of the Eastern Roman Empire that are rich in environmental, historical and archaeological data. The paper starts with the review of current research on the economic, settlement and vegetation history of the Eastern Mediterranean in Late Antiquity, which provides the necessary framework for the study of potential climate impacts. The core of the article is devoted to the analysis of the palaeoclimatic evidence, which is divided in two groups. The first one encompasses the direct evidence, that is palaeoclimate proxies and the textual record of extreme weather events, while the second includes indirect information on climate, in particular multi-proxy studies that include pollen analysis, archaeological evidence, and the historical evidence of subsistence crises. We conclude that during our study period there occurred three periods of substantially different climatic conditions. A late Roman drought ∼350–470 AD was followed by a dramatic shift to much wetter climatic conditions. These in turn changed into increasing dryness after ∼730 AD in Anatolia and ∼670 AD in the Levant. The lack of chronological precision in the dating of the archaeological evidence and of some climatic records makes it impossible at present to make conclusive observations regarding the societal responses to these climatic fluctuations. Nonetheless in all probability, the extended and – in some areas - severe late Roman drought did not cause any major social upheaval or economic decline in Anatolia or the Levant, although it appears to have contributed to a change in patterns of water use in the cities. In contrast, the increased availability of moisture after ∼470 AD does appear to have contributed to the expansion of rural settlement and agriculture into environmentally marginal terrain, including semi-arid areas such as the Negev. In this way climate probably contributed to the general economic prosperity of the late Roman Empire in the east of the Mediterranean basin. The end of this late Roman world system came about finally in mid-7th c. and, at least in Anatolia, is not directly associated with any shift in climatic conditions. Aridity during early Medieval times may be one of the main factors behind the gradual long-term decline of settlement on the marginal lands in the Levant following Islamic conquest. •We review different types of evidence for climate change in Anatolia and the Levant.•A drought (~350–470AD) contributed to local famines and a change in urban water use.•A wetter period after ~470 AD correlates with settlement expansion in arid lands.•Another drier phase occurred already after the crisis caused by the Arab invasions.•It contributed to the long-term settlement decline in some parts of the region.