Paleoneurological studies of mosasaurids are few and limited to old partial reconstructions made from latex casts on Platecarpus and Clidastes. Here, the brain endocasts of three specimens of the early mosasaurid Tethysaurus nopcsai from the Turonian of Morocco are reconstructed for the first time by using micro-computed tomography. Comparisons between Tethysaurus and the later Platecarpus and Clidastes show that distinct endocranial organizations have occurred within the clade through time, including differences in the flexure of the endocast and the size of the parietal eye. The physiological consequences of such variability remain unclear and further investigations are required to better interpret these variations. In addition, the endocast of Tethysaurus was compared to those of extant anguimorphs, iguanians, and snakes, using landmark-based geometric morphometrics. The results revealed that Tethysaurus exhibits a unique combination of endocranial features compared to extant toxicoferans. Contrary to previous statements, we find no strong resemblance in endocast morphology between Tethysaurus and varanids. Rather, the endocast of Tethysaurus shows some morphological similarities with each of the clades of anguimorphs, iguanians, and snakes. In this context, while a notable phylogenetic signal is observed in the variability of squamate endocasts, it is premature to establish any phylogenetic affinities between mosasaurids and extant squamates based solely on endocast morphologies.