Distinctive characteristics (synapomorphies) of Metatheria include a prehensile tail, the development of a capitular tail on the humerus, the loss of tooth replacement on the second and fifth premolars, lower canines that outwardly diverge from each other, an angular process on the dentary bone—which additionally bears a posterior shelf in its masseteric fossa in Metatheria[4]—that is equal to or greater than the length of the ramus,[4][5]: Appendix 2  and the lower fifth premolar with a "very trenchant"[4] cristid obliqua/ectolophid.

[7] The earliest possible known metatherian is Sinodelphys szalayi, which lived in China during the Early Cretaceous around 125 million years ago (mya).

[3] Metatherians were widespread in Asia and North America during the Late Cretaceous, including both Deltatheroida and Marsupialiformes,[10] with fossils also known from Europe during this time.

The oldest known Australian marsupials are from the early Eocene, and are thought to have arrived in the region after having dispersed via Antarctica from South America.

[11] Below is a metatherian cladogram from Wilson et al. (2016):[15] Holoclemensia Pappotherium Sulestes Oklatheridium Tsagandelta Lotheridium Deltatheroides Deltatheridium Nanocuris Atokatheridium Gurlin Tsav skull Borhyaenidae Mayulestes Jaskhadelphys Andinodelphys Pucadelphys Asiatherium Iugomortiferum Kokopellia Aenigmadelphys Anchistodelphys Glasbius Pediomys Pariadens Eodelphis Didelphodon Turgidodon Alphadon Albertatherium Marsupialia Cladogram after[16]:Deltatheriidae Kokopellia Asiatherium Peradectidae Stagodontidae Pucadelphyidae Sparassodonta Amphiperatherium Peratherium Herpetotherium Marsupialia