Fossils of Andrewsarchus have been recovered from the Middle Eocene Irdin Manha, Lushi, and Dongjun Formations of Inner Mongolia, each dated to the Irdinmanhan Asian land mammal age (Lutetian–Bartonian stages, 48–38 million years ago).

Andrewsarchus has historically been reputed as the largest terrestrial, carnivorous mammal given its skull length of 83.4 cm (32.8 in), though its overall body size was probably overestimated due to inaccurate comparisons with mesonychids.

Unlike many modern scavengers, a reduced sagittal crest and flat mandibular fossa suggest that Andrewsarchus likely had a fairly weak bite force.

[7] It was recovered from the lower Irdin Manha Formation of Inner Mongolia during a 1923 palaeontological expedition conducted by the American Museum of Natural History of New York.

Its generic name honours Roy Chapman Andrews, the leader of the expedition, with the Ancient Greek archos (ἀρχός, "ruler") added to his surname.

[1] A second species of Andrewsarchus, A. crassum, was named by Ding Suyin and colleagues in 1977 on the basis of IVPP V5101,[11] a pair of teeth (the second and third lower premolars) recovered from the Dongjun Formation of Guangxi.

[13] Comparisons between the two genera were drawn as far back as 1969, when Frederick Szalay suggested that they either evolved from the same arctocyonid ancestors or that they were an example of convergent evolution.

[1] However, considering cranial and dental similarities with entelodonts, Frederick Szalay and Stephen Jay Gould proposed that it had proportions less like mesonychids and more like them, and thus that Osborn's estimates were likely inaccurate.

[2] The holotype cranium of Andrewsarchus demonstrates the typical placental tooth formula, of three incisors, one canine, four premolars and three molars per side,[2] though it is not clear whether the same applies to the mandible.

[1] Their roots are not confluent and lack a dentine platform, which are both likely to be adaptations to prolong the tooth's functional life after crown abrasion.

Modern mammalian orders including the Perissodactyla, Artiodactyla, and Primates (or the suborder Euprimates) appeared already by the Early Eocene, diversifying rapidly and developing dentitions specialized for folivory.

The omnivorous forms mostly either switched to folivorous diets or went extinct by the Middle Eocene (Lutetian–Bartonian, 48–38 million years ago) along with the archaic "condylarths".

By the Late Eocene (Priabonian, 38–34 million years ago), most of the ungulate form dentitions shifted from bunodont cusps to cutting ridges (i.e. lophs) for folivorous diets.

[24][25] The Irdin Manha Formation, from which the holotype of Andrewsarchus was recovered, consists of Irdinmanhan strata dated to the Middle Eocene.

The mesonychid Mesonyx, the pantodont Eudinoceras, the dichobunid Dichobune, the helohyid Gobiohyus, the brontotheres Rhinotitan and Microtitan, the perissodactyls Amynodon and Lophialetes, the ctenodactylid Tsinlingomys, and the lagomorph Lushilagus have been identified from the Lushi Formation.

Protitan, the deperetellids Deperetella and Teleolophus, the hyracodontid Forstercooperia, the rhinocerotids Ilianodon and Prohyracodon, and the amynodonts Amynodon, Gigantamynodon, and Paramnyodon.