Livestock grazing and fire influence the composition of desert grassland communities, including their rodent populations. However, there have been few studies of the interactions between grazing and wildfire in arid grasslands of the southwestern United States. We trapped rodents and measured vegetation on grazed versus ungrazed plots before (2001) and following (2002–2007) an intense 15,000 ha wildfire in southeastern Arizona. The fire reduced grass canopy on grazed plots for 2 y and on ungrazed plots for 3 y. Some rodents in the family Cricetidae (genera Baiomys, Reithrodontomys and Sigmodon) were more abundant on ungrazed plots before the fire. Cricetidae as a whole declined following the fire and did not return to preburn levels until the sixth postfire year (2007). Nine of ten cricetid species contributed to this general pattern. By contrast, the abundant species of Heteromyidae (Chaetodipus hispidus, C. baileyi, Perognathus flavus) increased following the fire, especially on ungrazed plots. These results are consistent with a model predicting that fire-caused reductions in grass cover should favor Heteromyidae over Cricetidae. Fires elsewhere in the Southwest have had little impact on rodent populations, but these were smaller and cooler burns with relatively minor effects on vegetation. Future studies of large wildfires of varying intensities would further elucidate the generality of the model.