Mammals did not evolve from any modern group of reptiles. Soon after the first reptiles appeared, they split into two branches, the sauropsids and the synapsids.] The line leading to mammals diverged from the line leading to modern reptilian lines (the sauropsids) about 320 million years ago, in the mid Carboniferous period. Only later (in the late Carboniferous or early Permian) did the modern reptilian groups (lepidosaurs, turtles and crocodiles) diverge. The mammals themselves, being the only survivors of the synapsid line, are the "cousins" rather than "siblings" of modern reptiles.

Mammals are the only living synapsids. The synapsid lineage became distinct from the sauropsid lineage in the late Carboniferous period, between 320 and 315 million years ago.

After the Cretaceous-Paleogene extinction event wiped out the non-avian dinosaurs (birds are generally regarded as the surviving dinosaurs) and several other mammalian groups, placental and marsupial mammals diversified into many new forms and ecological niches throughout the Paleogene and Neogene, by the end of which all modern orders had appeared.

Most of the evidence consists of fossils. For many years, fossils of Mesozoic mammals and their immediate ancestors were very rare and fragmentary; but, since the mid-1990s, there have been many important new finds, especially in China. The relatively new techniques of molecular phylogenetics have also shed light on some aspects of mammalian evolution by estimating the timing of important divergence points for modern species. When used carefully, these techniques often, but not always, agree with the fossil record.

Although mammary glands are a signature feature of modern mammals, little is known about the evolution of lactation. This is because these soft tissues are not often preserved in the fossil record. Most study of the evolution of mammals centers, rather, around the shapes of the teeth, the hardest parts of the tetrapod body. Other much-studied aspects include the evolution of the middle ear bones, erect limb posture, a bony secondary palate, fur, and hair, and warm-bloodedness.