The physical nature of water and the environment it presents to an organism have long been recognized as important constraints on aquatic adaptation and evolution. Little is known about the dermal cover of mosasauroids (a group of secondarily aquatic reptiles that occupied a wide array of predatory niches in the Cretaceous marine ecosystems 92-65 Myr ago), a lack of information that has hindered inferences about the nature and level of their aquatic adaptations. A newly discovered Plotosaurus skeleton with integument preserved in three dimensions represents not only the first documented squamation in a mosasaurine mosasaur but also the first record of skin in an advanced member of the Mosasauroidea. The dermal cover comprises keeled and possibly osteoderm-reinforced scales that presumably contributed to an anterior-posterior channelling of the water flow and a reduction of microturbulent burst activities along the surface of the skin. Thus, hydrodynamic requirements of life in the water might have influenced the evolution of multiple-keeled body scales in advanced mosasauroids.