Glyptosaurinae is an extinct subfamily of lizards of the family Anguidae. Glyptosaurine lizards are known exclusively from the Paleogene of North America and Eurasia, reaching their peak of diversity and distribution in the Eocene. In North America these lizards are largely restricted to the intermontane basins along the Rocky Mountain range, with only sparse, indeterminately-identified skeletal elements known from outside of this region. Glyptosaurine lizards are split into two tribes: the monophyletic Glyptosaurini and paraphyletic “Melanosaurini”. Within Glyptosaurini, the most common and widespread genus is Glyptosaurus. In this study I describe a new specimen assignable to G. sylvestris, notable for being recovered from the late Uintan of the Santiago Formation in southern California, significantly outside the typical known geographic range of well-preserved glyptosaurine fossils. The presence of Glyptosaurus in southern California at a time of widespread tectonic and climatic change and increasing regional endemism in mammalian faunas, when also considering the results other studies of Eocene lizards, indicates a pattern of evolution for lizards of the time that is quite different from the dramatic turnovers and regional restrictions observed in Eocene mammals. The specimen described here also shows features consistent with ontogenetic variation and may help to provide insight into the life history of glyptosaurine lizards.