Understanding how organisms adapt to aridity is a central theme in traditional desert ecology research. However, many of the pioneering studies were conducted before detailed phylogenies were available to provide evolutionary context and before the accumulation of accurate bioclimatic and species distribution data to provide geographic and environmental context. We tested the desert-adaptive value of changes in skull and dental morphology in rodents after phylogenetic correction. In addition, we estimated that across the evolutionary history of more than 2,400 rodent species, transitions between mesic and desert habitats have been very frequent, with a directional bias toward the mesic-to-desert transition. This suggested that derived desert specialization is an “evolutionary deadend” that limits further evolution. After correcting for the strong phylogenetic signal, we still find a significant and strong correlation between habitat aridity and specializations associated with auditory sensitivity (auditory bulla inflation) and respiratory water retention (nasal passage elongation) but not in characters associated with dietary specialization (lower incisor shape). No other significant associations were found between habitat or aridity and any other cranial, jaw, or dental traits. Bullar hypertrophy is among the strongest patterns of convergent cranial desert adaptation in rodents and indicates that adaptation plays a similar role in shaping the evolution of this structure in different desert rodent clades.