Exploring the relationship between personality and well-being is of great significance for both individual development and social progress. However, directly generalizing findings from individual-level studies to group-level contexts may lead to ecological fallacies. The emergence of geographical psychology offers a new perspective for uncovering how clusters of personality interact with well-being outcomes. Therefore, this study conducted a correlational analysis of personality and well-being across the 50 U.S. states, revealing the associations between regional personality clusters and well-being indicators. The results show that neuroticism is significantly negatively correlated with most well-being indicators; for instance, neuroticism is negatively correlated with Gallup’s overall well-being (r = − 0.623, p < 0.001). After controlling for variables, extraversion is positively correlated with emotional health-related well-being (r = 0.438, p < 0.01) and other aspects as well, but negatively correlated with happiness on Twitter (r = − 0.303, p < 0.05). Agreeableness is positively correlated with work environment-related well-being (r = 0.465, p < 0.01) and shows similar trends in other dimensions. Conscientiousness is positively correlated with life evaluation-related well-being (r = 0.395, p < 0.01) and also demonstrates positive correlations in other aspects. Openness to experience is positively correlated with health behavior-related well-being (r = 0.542, p < 0.001) and shows positive associations with other relevant indicators as well. This study enhances our understanding of the interplay between regional personality and the socio-economic environment in shaping population well-being, providing scientific guidance for interventions that respect cultural and environmental diversity within nations.