A new plagiolophine equoid from the Eocene of the Iberian Peninsula, Iberolophus gen. nov., is herein reported. This new genus includes two species: I. arabensis sp. nov. (type species) from the Late Eocene (Headonian) of Zambrana (Araba, Basque Country) and I. jimenezi sp. nov. from the late Middle Eocene (Robiacian) of Mazaterón (Soria, Castilla y León). Iberolophus exhibits an unusual dental pattern that has not yet been reported in any other perissodactyl or ungulate to date. A complete (with P1/p1) and very long non-lophoid premolar series, in which premolars exhibit one (in the earlier members) or two (in the later members) high and pointed cusp(s) anteriorly and a low and long backward extended talon/talonid posteriorly, with a bumpy surface texture, is combined with a typical plagiolophine type lophodont and heterodont molar series. The new taxa are ranked as members of the endemic fauna of the Western Iberian Bioprovince. The latter includes the Eocene sites of the central and western Iberian basins (Duero, Almazán, Oviedo, and Miranda-Trebiño Basins), which have yielded Middle and Late Eocene mammal fossil assemblages (mainly perissodactyls, rodents and primates) which differ from those of the Southern Pyrenean Basins and the rest of Europe. The endemism of the perissodactyl faunas persisted during the Late Eocene in the central and western Iberian basins, on the basis that the perissodactyl fossils from the middle Headonian beds at Zambrana (Miranda-Trebiño Basin) are related to endemic taxa from the late Robiacian beds of the Duero, Almazán, and Oviedo Basins.