The genus is noted for its large size, with Macroeuphractus outesi being the largest non-pampathere or glyptodont armadillo discovered, as well as its specializations for carnivory, unique among all xenarthrans.

The most recent phylogenetic examinations confirm its status as at least a sister group to euphractines, along with Paleuphractus, Doellotatus and Proeuphractus.

Species like Macroeuphractus outesi were fairly large and presumably had an apex predator status in their faunal communities.

The genus occurs in an epoch where sparassodonts, phorusrhacids and sebecids entered in decline, and was among the various mammal groups to exploit this ecological vacancy prior to the arrival of North American carnivorans in the Pleistocene, alongside giant opossums such as Thylophorops.

[9] Nonetheless, Macroeuphractus still co-existed with late surviving sparassodonts such as Thylacosmilus and phorusrhacids like Llallawavis.