The taxonomy and dental evolution of cotton rats, genus Sigmodon, from Pliocene and Pleistocene deposits in the Meade Basin of southwestern Kansas are examined. Prosigmodon is here subsumed under Sigmodon. Morphological and multivariate statistical analyses identify 3 Sigmodon lineages and 5 immigration events in the Meade Basin. The 1st immigration event occurred during the early Blancan and the latest during the Holocene. The analyses of dental characters indicate directional trends in almost all features, representing both size and shape. A comparison of information from the cotton rat fossil record with a recent molecular phylogeny suggests the molecular phylogeny has set the origin of modern cotton rat groups too early. North American species groups probably do not predate the late Pliocene.