Amik Lake or, historically, Lake of Antioch, was a large freshwater body in the lower Orontes River basin (Hatay Province, Turkey) that was drained in the 1940s–1970s. Several endemic animal species were described from this lake, including the freshwater mussel Anodonta pseudodopsisLocard, 1883 (Bivalvia: Unionidae) characterized by a large rounded shell covered by a peculiar yellow or yellowish-brown periostracum. Molecular analyses of topotypes of this nominal taxon collected from the former lake’s tributaries in the Amik Plain indicate that it is an intra-specific lineage of the widespread Anodonta anatina (Linnaeus, 1758) based on the mitochondrial COI and 16S rRNA, and the nuclear 28S rRNA gene fragments. Geometric morphometric analyses using the lectotype and topotypes of Anodonta pseudodopsis support our DNA-based hypothesis on the status of this nominal taxon. A new synonymy is provided as follows: Anodonta anatina = Anodonta pseudodopsissyn. nov. The syntype of Anodonta pseudodopsis SMF 5129 “See von Antiochia” (Senckenberg Research Institute and Natural History Museum, Frankfurt, Germany) is designated here to be the lectotype of this nominal taxon. Finally, we conclude that Anodonta anatina range covers the Orontes River basin in Turkey and Syria and the Nahr al-Kabir al-Shamali River in the Latakia Governorate of Syria. This intraspecific lineage of Anodonta anatina and other freshwater mussels of the Middle East are highly threatened due to multiple anthropogenic impacts and must be a focus of international conservation efforts. The Karasu River in eastern Turkey hosts viable populations of all freshwater mussel species of the Orontes’s fauna and can be considered one of the most important water bodies for the conservation of these imperiled animals in the region.