The Meade Basin, SW Kansas, yields a rich vertebrate fossil record from the late Cenozoic. Here, we review fossil ground squirrels (Sciuridae) from the region as a contribution to the broader Meade Basin Rodent Project. We recognize 14 species in seven genera: two species of giant ground squirrels (Paenemarmota Hibbard and Schultz, 1948) from the early Pliocene, and at least 12 species in six extant genera (Ammospermophilus Merriam, 1892; Otospermophilus Brandt, 1844; Ictidomys Allen, 1877; Poliocitellus Howell, 1938; Urocitellus Obolenskij, 1927; Cynomys Rafinesque, 1817) from the Pliocene—Pleistocene sequence, including the first regional records of Ammospermophilus. Based on dental morphology and the ecology of modern congeners, we interpret faunal change through the sequence as primarily reflecting a shift from a Pliocene assemblage of “southwestern” taxa with granivorous/omnivorous diets (relatively low-crowned, transversely narrow cheek teeth) in warm and at least occasionally dry shrub or shrub-steppe habitats (Ammospermophilus, Otospermophilus, Ictidomys meadensis [Hibbard, 1941a]), to a Pleistocene temperate assemblage of grazing taxa that either exhibited relatively high-crowned, transversely wider cheek teeth (Urocitellus, Cynomys, Ictidomys tridecemlineatus [Mitchill, 1821]) or were otherwise dependent on grassland habitats (Poliocitellus). The early Pleistocene Borchers assemblage was transitional in this regard, heralding a “revolution” observed as well with other clades in the Meade Basin rodent community. This interpretation is broadly congruent with evidence of Pliocene climatic change and the staged development of regional grasslands, with the modern proportion of C3/C4 plants established in the Meade Basin during the early Pleistocene.