The braincase of two acid-prepared specimens of Nothosaurus is described in detail and compared to the braincase of Simosaurus, the sister-group of the Nothosauridae and Cymatosaurus. Nothosaurus is characterized by a number of derived neurocranial characters, which diagnose a monophyletic family Nothosauridae. The family includes the genera Nothosaurus, Paranothosaurus (possibly congeneric with Nothosaurus), Ceresiosaurus, and Lariosaurus. The sister-group of the Nothosauridae is Cymatosaurus.
In comparison to its sister-group (Cymatosaurus), the Nothosauridae are characterized by an extreme dorsoventral flattening of the temporal region of the skull. This is correlated with the development of an occipital flange on the squamosal and parietal, allowing posterodorsal expansion of the jaw adductor musculature. A ventromedial flange along the quadrate ramus of the pterygoid indicates an increase in size of M. pterygoideus internus.