The John Day Formation of Oregon is one of the richest and best studied assemblages in North America. Including seven members and spanning about 20 million years, there are over 150 vertebrate species known from the John Day Formation. The rodent faunas of John Day have not been as well studied as larger mammals, with many families having received little attention in the last hundred years. Here, twenty one species of rodents are described, based on new discoveries and previously unpublished specimens from the John Day Formation. The new material includes four new genera and species; the eutypomyid Allotypomys pictus, the anchitheriomyine castorid Microtheriomys brevirhinus, the eomyid Proapeomys condoni, the heteromyid Bursagnathus aterosseus; and six new species: the sciurine sciurid Miosciurus covensis, the eomyids Apeomys whistleri and Neoadjidaumo arctozophus, the heteromyids Proheteromys latidens and Trogomys oregonensis, and the sicistine dipodid Plesiosminthus fremdi. The problematical eomyid species, “Florentiamys” lulli Wood, 1936a, is referred questionably as a new combination, ?Proapeomys lulli (Wood, 1936a). Emended diagnoses of Miosciurus ballovianus (Cope, 1881) and Proheteromys thorpei Wood, 1935b, are offered based upon substantially more complete material than was previously known for either. Biostratigraphic ranges of the newly described rodents allow more direct comparison with other contemporaneous faunas from North America. These new rodents also allow better reconstruction of past ecosystems and are vital for understanding how faunas have changed through time in the region.