Urbanization is a selective force that is known to drive changes in the population dynamics of wildlife. How animals adapt to changing environmental conditions is crucial to their survival in these environments. Relative brain size, or cranial capacity, is a known proxy of behavioral flexibility, and can be used to assess how well a species has adapted to a particular environment. We examined changes in cranial capacity in a time series of small mammal skulls collected from urban and rural populations in southwestern Pennsylvania. Skulls from urban populations were collected from Allegheny County, an area that experienced rapid urbanization over the past century, and skulls of rural populations from the Powdermill Nature Reserve of the Carnegie Museum, which has remained relatively unchanged forest over the same period. Our results show that Peromyscus leucopus and Microtus pennsylvanicus from urban populations had significantly greater cranial capacity than their rural counterparts, but the opposite was true for Eptesicus fuscus. We found no difference in relative cranial capacity across time in any of the small mammal species. Our results suggest that a larger cranial capacity is selected for in an urban environment and reinforces the hypothesis that behavioral flexibility is important for animals to adapt to novel environments.