Diachronic analyses of regional settlements patterns have proven to be useful for analysing relations between humans and the environment and highlighting choices of settlements locations and land exploitation. A set of methods and data, such as archaeological, geomorphological, historical data, and quantitative methods, can be used to understand changes in the archaeological landscapes through time. While this approach is a standard in many recent regional studies, older surveys and excavation data still need to be brought in line with more interdisciplinary studies. This paper will explore the possibilities of a diachronic and multidisciplinary approach applied to the so-called Syrian Middle Euphrates, extending roughly from Deir ez-Zor to Abu Kemal on the Syrian-Iraqi border. The analysis will focus on Iron Age settlement patterns, but it will explore earlier and later periods as well, in order to understand and highlight changes through time. The analysis will also use remote sensing to highlight and analyse landscape features and the effects of land exploitation on the archaeological landscape through time.