Based on the unequaled southern Late Cretaceous–Cenozoic record, the history of South American land mammals is divisible into two major episodes we term the Gondwanan Episode and the South American Episode. The former episode is distinguished by the northern and central Patagonian Argentinian record, while the latter is mostly based on the extra-Patagonian Argentinian record. The Gondwanan Episode is so termed because it is exclusively represented by endemic mammals of Gondwanan origin, i.e., Mesozoic lineages. In contrast, the South American Episode is almost exclusively distinguished by endemic Therian mammals whose ancestors emigrated from the Laurasian North American Continent.

These two major, successive, and for some time superimposed episodes are the result of the geologic history of the South American Plate. (1) This plate was part of the Gondwana Supercontinent until about 120 millions of years before Present (mybP), when it began to separate and drifted westward (but always south and relatively near the North American Plate). Until about 30 mybP it was connected to Western Antarctica, and through it to most of the Eastern Gondwanan continents. (2) By approximately 125 mybP, Donnelly's “Flood Basalt” was initiated. After its cessation by 85 mybP a variety of compressive tectonic features around the Caribbean began, i.e., subduction and island arcs or continental margin magmatism. These features probably permitted the first known inter-American exchange of tetrapods, dinosaurs such as Hadrosauridae from the rising North American continent and Titanosauridae Saltasaurinae from the South American continent. Probably by the latest Cretaceous these geologic features also permitted the immigration of the first Therian, which gave rise to the native South American land mammals. (3) The geologic definition of southern Central America is the last and most important phenomenon related to the final connection of both Americas. By 12 mybP the submarine connection of Central America with South America began, and subsequent volcanic island arcs permitted the beginning of The Great American Biotic Interchange.

According to the Patagonian record, the absence of tribosphenic mammals and the total extinction of the endemic non- and pre-tribosphenic mammals are the most outstanding events characterizing the Gondwanan Episode. Up to the beginning of the South American Episode (early Paleocene), few Gondwanan lineages of mammals (a native Gondwanatheria and an endemic Dryolestoid) survived in the South American continent; another related Gondwanatheria taxon survived up to the Late Eocene in Western Antarctica. These Gondwanan survivors lived together with the first, but advanced, immigrant Therian that initiated the South American Episode. Although not conclusively demonstrated, there are some suggestions that this superposition began earlier, probably by the pre-Campanian Cretaceous. The history of endemic Therian mammals characterizing the South American Episode began to be known in 1948 thanks to the efforts of the Ameghinos and G. G. Simpson. These represented the only known higher taxa until 1985 when Bonaparte recorded the first non-therian Gondwanan lineages in Late Cretaceous (Campanian) Patagonian beds. Successive authors contributed to this history, ratifying Simpson's statement that the South American Cenozoic mammal evolution was episodic. Thus, the most characteristic geobiotic features of the two major episodes are based almost exclusively on the most eloquent Campanian-Quaternary Argentinian record.