There is overwhelming evidence for regional variation across the United States on a range of key political, economic, social, and health indicators. However, a substantial body of research suggests that activities in each of these domains are typically influenced by psychological variables, raising the possibility that psychological forces might be the mediating or causal factors responsible for regional variation in the key indicators. Thus, the present article examined whether configurations of psychological variables, in this case personality traits, can usefully be used to segment the country. Do regions emerge that can be defined in terms of their characteristic personality profiles? How are those regions distributed geographically? And are they associated with particular patterns of key political, economic, social, and health indicators? Results from cluster analyses of 5 independent samples totaling over 1.5 million individuals identified 3 robust psychological profiles: Friendly & Conventional, Relaxed & Creative, and Temperamental & Uninhibited. The psychological profiles were found to cluster geographically and displayed unique patterns of associations with key geographical indicators. The findings demonstrate the value of a geographical perspective in unpacking the connections between microlevel processes and consequential macrolevel outcomes.