The salamander Eoscapherpeton asiaticum from the Upper Cretaceous of Uzbekistan is one of the most basal cryptobranchids and provides important information on the early evolution of Cryptobranchidae. We describe the cranial anatomy of E. asiaticum based on computed tomography of several specimens. The skull is not as dorsoventrally flattened as in extant cryptobranchids. The skull is further characterized by: ventrolaterally oriented suspensorium; extensive squamosal–parietal contact; long vomeral process of the premaxilla; septum in the olfactory region, formed by the dorsal processes of the vomers; complex system of neurovascular canals in the premaxillae, maxillae, frontals, and mandible; extensively ossified hyobranchial apparatus; presence of lacrimals, anterior coronoids, and large pterygoids; and absence of anteromedial fenestra in the palate. The cranial structure (ossified hyobranchial apparatus; complex system of neurovascular canals; subhorizontal ridge on labial surface of premaxilla and maxilla; and lack of anteromedial fenestra) suggests that E. asiaticum was an active aquatic predator that used the well-developed lateral line system in its head as a unique adaptation for locating prey. The acquisition of large body size in derived species of Cryptobranchidae, together with retaining the neotenic state, led to the flattening of the skull and the origin of a complex suction-feeding mechanism characteristic of extant cryptobranchids.