Glyptosaurines are an extinct clade of anguids whose remains are common in many Holarctic Paleogene and Cretaceous deposits. Despite their extensive fossil record (comprised mainly of scutes) the braincase is poorly known. Here, we describe braincase morphology in two North American Eocene glyptosaurines, Melanosaurus maximus and Helodermoides tuberculatus. Although generally conservative in their braincase morphology compared with other anguids, these taxa and some other “higher” glyptosaurines possess a dorsally displaced parasphenoid rostrum. The anterior openings for the Vidian canals open almost directly ventral to the parasphenoid rostrum, and the internal carotids exit anteriorly almost directly dorsal to it. Our phylogenetic analysis recovers a monophyletic Glyptosaurinae nested within Anguidae as the sister taxon to a clade containing Gerrhonotinae and Anguinae. According to our analysis, “melanosaurins” are paraphyletic, Placosaurus is paraphyletic, and Anniella is the sister taxon to Anguis.