Mesosaurus (meaning "middle lizard") is an extinct genus of aquatic reptile from the late Early Permian (Kungurian, ~275 million years ago) of southern Africa and South America. It is the only member of the family Mesosauridae and order Mesosauria. Two other genera of mesosaurs, Brazilosaurus and Stereosternum, were formerly recognised, but are now considered synonyms of Mesosaurus. Mesosaurus contains a single valid species, M. tenuidens. Mesosaurus represents one of the earliest lineages of aquatically adapted reptiles. It had many adaptations to a fully aquatic lifestyle. Mesosaurus lived around the shorelines of the Irati–Whitehill sea, an epicontinental sea that covered parts of southern Pangaea during the late Early Permian, likely feeding on small prey such as pygocephalomorph crustaceans. Mesosaurs have often been considered parareptiles, though the validity of "Parareptilia" has recently been brought into question. Recent studies regardless place mesosaurs as basal, non-diapsid reptiles.

The holotype of M. tenuidens, MNHN 1865–77, is nicknamed the "Griqua Mesosaurus" and it was found in a Griqua hut in South Africa, likely in Kimberley, Northern Cape around 1830 and was being used as a pot lid. The circumstances of its discovery and how it was taken from its previous owners in South Africa are unknown, but what is known is that the specimen eventually surfaced in the collection of the French palaeontologist Paul Gervais during the 1860s and he designated it as the holotype of a new genus and species he named Mesosaurus tenuidens in 1865. In 1889, the species Ditchrosaurus capensis was named by Georg Gürich based on remains found in South Africa, though this is now regarded as a synonym of M. tenuidens. Since then, Mesosaurus remains have also been identified from South America and were first identified in 1908 as belonging to a second species, M. brasiliensis, by J. H. MacGregor. Later studies have shown that M. brasiliensis is another synonym of M. tenuidens.

Two other species of mesosaurs have been described and historically considered valid; Stereosternum tumidum and Brazilosaurus sanpauloensis. Stereosternum tumidum was named by Edward Drinker Cope in 1886, based on specimens he studied while Brazil, in the collections of the Museu Nacional (Rio de Janeiro). Brazilosaurus is known from specimen BSPG 1965 I 131, a single skeleton recovered from the Assistencia Member of the Irati Formation (Hanayama Farm, Tatuí, São Paulo), in the Paraná Basin. It was named by T. Shikama and H. Ozaki in 1966.

Stereosternum, Brazilosaurus & Mesosaurus were historically regarded as valid genera, distinguished by the shape of their teeth. However, recent studies have suggested that the teeth actually changed shape of the course of growth, and that only Mesosaurus is actually a valid genus, with the other two genera representing juvenile or fragmentary specimens of Mesosaurus, and that M. tenuidens represents the only valid mesosaur species.

Mesosaurs have been described as small-medium-sized reptiles, with hatchlings around 10–12 centimetres (3.9–4.7 in) long, and young adult specimens around 80–90 centimetres (31–35 in) in length, with most collected specimens being around 70 centimetres (28 in). The largest known individuals are estimated to have reached a length of 1.5 to 2.5 metres (59 to 98 in), though such specimens are rare as fossils, perhaps because large individuals had different environmental preferences than younger individuals.

The bodies of mesosaurs are slender with an elongate tail, which was proportionally narrow from side to side. The bones exhibit pachyosteosclerosis (the property of being both thick and relatively dense). The limbs are paddle-like, with preserved soft tissue from some individuals indicating that the feet were webbed. Mesosaurus is unusual among reptiles in that it possesses a cleithrum, usually found in more primitive bony fish and tetrapods. The head of the interclavicle of Mesosaurus is triangular, unlike those of other early reptiles, which are diamond-shaped.

The rostrum (the front part of the skull) is relatively elongate and the jaws exhibit numerous slender, conical teeth, which underwent replacement, as well as palatal teeth at the roof of the mouth. Mesosaurus possessed a smooth enamel-dentine junction, reflecting its enamel being solely formed by cells of the ectoderm. The nostrils were located at the top, allowing the creature to breathe with only the upper side of its head breaking the surface, in a similar manner to a modern crocodile. The back of the skull exhibits a single pair of lower temporal fenetestrae. Over the course of growth, the skull became proportionally shorter though the proportion made up by the snout increased due to elongation, the teeth became more elongate and the hindlimb and the forelimb hand (manus) became proportionally shorter.

Mesosaurus had a small skull with long jaws. The teeth were originally thought to have been straining devices for the filter feeding of planktonic organisms. However, this idea was based on the assumption that the teeth of Mesosaurus were numerous and close together in the jaws. Newly examined remains of Mesosaurus show that it had fewer teeth and that the dentition was suitable for catching small (under 2 centimetres (0.79 in) in length) nektonic prey such as crustaceans, specifically those belonging to the extinct order Pygocephalomorpha, which were abundant in the environment in which Mesosaurus lived (which are otherwise scarce in fossils) and have been found in coprolites (fossilised feces) attributed to Mesosaurus. Mesosaurus may also have engaged in cannibalism, based on remains of juvenile mesosaurs found in coprolites and regurgitates attributed to mesosaurs. These however may be a result of scavenging rather than active predation.