[14] Amphimachairodus has been suggested to be a paraphyletic evolutionary grade that evolved from species of the genus Machairodus, and is in turn ancestral to later homotherines like Homotherium.

[16] The species Amphimachairodus coloradensis, from the United States was a significantly large animal, about 1.2 m (3.9 ft) at the shoulder, according to skeletal and life reconstructions, potentially making it one of the largest known felids.

[17] All Amphimachairodus species have a developed mandibular flange, however, A. colaradensis is distinguishable from A. giganteus and A. kurteni by subtle differences in the shape of the mandible and placement of lower carnassials.

In size and proportions, the Eurasian species A. giganteus was remarkably similar to a modern lion or tiger and had a shoulder height of 1.1 m (3.6 ft).

[23] Deformation of the skull through natural fossilization processes has changed the shape slightly, making it asymmetrical, but overall it remains an excellent specimen for studying the cranial morphology of this particular genus and species.

Compared with the most well known machairodont Smilodon, commonly referred to as the "saber-toothed cat", the canines are much shorter, the facial portion again is much longer, and the teeth not reduced so far in number.

[29] At the Optima fossil site in Oklahoma isotopic analysis suggest a high degree of niche partitioning within the carnivore guild (Agriotherium, Borophagus, Eucyon, & the mustelid Pliotaxidea) with A. coloradensis having a preference for horses (61.4%) as opposed to camels, mastodons, pronghorns & rhinos (38.7%).

Amphimachairodus giganteus was an inhabitant of woodlands and open floodplains as based on finds in Pikermi in Greece and Shanxi Province in China, indicating it had habitat preferences similar to modern lions in many respects.

Among the creatures it shared its environment with were bovids such as Parabos, Lutung monkeys, the proboscidean Anancus, the rhino Aceratherium, antelopes such as Tragoportax and Miotragocerus as well as gazelles and deer, a very large species of hyrax, early goats, various giraffes, camels such as Paracamelus, the horse Hipparion, a species of aardvark, the chalicothere Ancylotherium and the beaver-like Dipoides.

Other carnivores it shared its territory with include the percrocutid Dinocrocuta, the bear Agriotherium, fellow machairodonts Metailurus and Paramachairodus and hyenas like Thalassictis.

In North America, in places such as Coffee Ranch in Texas, Amphimachairodus coloradensis shared territory with Agriotherium as it had in Africa and Eurasia, but also shared territory with the feliform Barbourofelis and the canids such as Vulpes, Epicyon and Borophagus, and herbivores like the camels Aepycamelus and Hemiauchenia the pronghorn antelope Cosoryx, horses like Dinohippus, Neohipparion and Nannippus, the peccary Prosthennops and rhinoceroses like Teleoceras and Aphelops.

[37][38] In the Djurab desert in northern Chad, Amphimachairodus kabir co-existed with fellow machairodonts Lokotunjailurus, Tchadailurus and early representatives of the genus Megantereon.

In addition, animals such as crocodiles, three-toed horses, fish, monkeys, hippos, aardvarks, turtles, rodents, giraffes, snakes, antelopes, pigs, mongooses, foxes, hyenas, otters, honey badgers and the hominid Sahelanthropus dwelled here, providing ample food.

[40][41] In the Late Miocene of the Tibetan Plateau, Amphimachairodus hezhengensis would have coexisted with a number of other large carnivores including two species of medium-sized bears, the barbourofelid Albanosmilus, fellow Machairodont Machairodus, and the huge hyena Dinocrocuta.