The present study entails descriptions of several well-preserved skulls from the pampathere species Holmesina floridanus, recovered from Pliocene localities in central Florida and housed in the collections of the Florida Museum of Natural History. Bone by bone descriptions have allowed detailed reconstructions of cranial morphology. Cranial foramina are described and illustrated in detail, and their contents inferred. The first ever description of an isolated pampathere petrosal is also included. Cranial osteology of Holmesina floridanus is compared to that of Pleistocene species of Holmesina from both North and South America (Holmesina septentrionalis, Holmesina occidentalis), as well as to the other well-known pampathere genera, to closely related taxa among glyptodonts (Propalaehoplophorus), and to extinct and extant armadillos (Proeutatus, Euphractus). This study identifies a suite of apomorphic cranial features that serve to diagnose a putative, progressive series of more inclusive monophyletic groups, including the species Holmesina floridanus, the genus Holmesina, pampatheres, pampatheres plus glyptodonts, and a clade formed by pampatheres, glyptodonts, and Proeutatus. The study highlights the need for further anatomical investigations of pampathere cranial anatomy, especially those using modern scanning technology, and for analyses of pampathere phylogenetic relationships.