The great North American Pleistocene pantherine felid Panthera atrox has had a turbulent phylogenetic history, and has been claimed to show affinities to both the jaguar and the tiger; currently, it is most often regarded as a subspecies of the extant lion. The cranial, mandibular, and dental morphology of Panthera atrox was compared with those of extant lions, jaguars, and tigers using bivariate, multivariate, and shape analyses. Results indicate that the skull of Panthera atrox shows lion affinities, but also deviates from lions in numerous aspects. Mandibular morphology is more similar to jaguars and tigers and, as with cranial morphology, the mandible shows a number of traits not present among extant pantherines. Multivariate analyses grouped Panthera atrox separately from other pantherines. Panthera atrox was no lion, and cannot be assigned to any of the extant pantherines; it constituted a separate species. A possible scenario for evolution of P. atrox is that it formed part of a pantherine lineage that entered the Americas in the mid-Pleistocene and gave rise to the extant jaguar and Panthera atrox in the late Pleistocene of North America. These studies suggest that previous models of lion biogeography are incorrect, and although lions may have been present in Beringia, they did not penetrate into the American mainland.