The genus was described based on a left fragment of a maxilla (upper jaw) from the Mazaterón Formation of the Duero Basin, from which its name derives, in 2009.

Its dentition is mostly typical of the Anoplotheriinae but differs from related genera in the elongated and triangular third upper premolar and traits of the molars.

The exact evolutionary origin of anoplotheriids remain uncertain, but they were exclusively distributed in Europe when it was an archipelago that was isolated by seaway barriers from other regions such as Balkanatolia and the rest of eastern Eurasia.

The Dacrytheriinae is the older subfamily and first appeared in the Middle Eocene (in the Mammal Palaeogene zones unit MP13, possibly up to MP10), although some authors consider them to be a separate family, as Dacrytheriidae.

After a significant gap of anoplotheriines in MP17a-MP17b, the derived anoplotheriids Anoplotherium and Diplobune made their first appearances by MP18, although their exact origins remain unknown.

[1] In 2022, Weppe published a phylogenetic analysis in his PhD thesis regarding Palaeogene artiodactyl lineages, focusing on the endemic European families.

In this tree, the Anoplotheriidae, Mixtotheriidae, and Cainotherioidea form a clade based on synapomorphic dental traits (newly evolved tooth features they have in common).

The subfamily Anoplotheriinae differs from the Dacrytheriinae by the molariform premolars with crescent-shaped paraconules and the lower molars that lack a third cusp between the metaconid and entoconid.

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.

[11] The Mazaterón Formation of the Duero Basin dates to the middle Late Eocene (Robiacian of Europe) and ranges in faunal level from MP15–MP16.

[1] The taxa known from the Mazaterón fossil site with Duerotherium include the testudines Hadrianus and Neochelys, alligatoroid Diplocynodon, baurusuchid Iberosuchus, adapoid Mazateronodon, omomyid Pseudoloris, pseudosciurid rodent Sciuroides, theridomyid rodents Pseudoltinomys and Remys, hyaenodont Proviverra, palaeotheres (Paranchilophus, Plagiolophus, Leptolophus, Palaeotherium, Cantabrotherium, Franzenium, and Iberolophus), dacrytheriines (cf.