An aquatic animal faces challenges not encountered by its terrestrial counterparts, promoting adaptive responses in multiple traits. For example, a thicker dermis might protect snakes when they are pushed against sharp objects by water currents, and might enable a snake to shed fouling organisms attached to its skin. We thus predicted that marine snakes should have thicker skin than terrestrial species, and that smaller sea snakes should have relatively thicker skin (because absolute, not relative, thickness determines vulnerability to fouling). Measurements of 192 snakes of 44 species supported those predictions. Many (but not all) sea snakes have skins 50% thicker than those of terrestrial and amphibious snake species, representing multiple independent evolutionary origins of thicker skin (in acrochordids, Laticauda sea kraits and both main clades of hydrophiine sea snakes). Marine snakes showed different allometries of skin thickness compared with their terrestrial counterparts; larger snakes had thicker skin within and among species of amphibious and terrestrial snakes, but larger aquatic snake species had thinner skin compared with smaller taxa. Interspecific variation in skin thickness was primarily due to increased collagen in the deep dermis, a physical barrier well suited to protecting against physical injury and to resisting penetration by epibionts.