Cylindrodontids are Eocene and Oligocene protrogomorphous rodents known from North America and Asia. Their oldest reported occurrence had been with North American Bridgerian Mysops. Earliest Wasatchian estuarine deposits at the Red Hot Truck Stop locality in the T4 sand, Tuscahoma Formation, near Meridian, Mississippi, have produced the oldest and most primitive cylindrodontids, having derived familial characters along with a generally primitive morphology. These are referred to three new species of the new genus Tuscahomys: T. medius, T. minor and T. major. These rodents inhabited an estuarine environment having paratropical climatic conditions. An additional species from the early Eocene of Wyoming, Reithroparamys ctenodactylops Korth, 1984, is referred to the new genus as Tuscahomys ctenodactylops (Korth, 1984), new combination.