The fertile alluvial plain of Cilicia is bordered by the Taurus and Amanus mountain ranges to the west, north and east and the Mediterranean Sea to the south. Since the Neolithic Period, Plain Cilicia was an important interface between Anatolia and the Levant. The alluvial plain is dominated by three rivers: Tarsus, Seyhan and Ceyhan. The avulsion history of the lower course of the rivers Seyhan and Ceyhan during the Holocene remains an unresolved issue. The knowledge about how former river courses have changed is essential for the identification of ancient toponyms with archaeological sites. The analysis of silted up riverbeds based on high-resolution digital elevation models (TanDEM-X) and historic satellite imagery (CORONA) in this paper provide the first indications for the reconstruction of former river channels. Further evidence is given by the evaluation of the settlement patterns from 3rd to 1st millennium BC.