ABSTRACT: Context:The increasing prevalence of overweight in youth has been well chronicled, but less is known about the unique patterns and risks that may exist in rural and urban environments. A better understanding of possible rural–urban differences in physical activity profiles may facilitate the development of more targeted physical activity interventions. Methods: Participants (1,687 boys; 1,729 girls) were recruited from fourth, fifth, and sixth grade classes in schools from urban areas, small cities, and rural areas. Multilevel modeling analysis was used to examine rural–urban differences in physical activity and prevalence of overweight. Physical activity was assessed by self-report and body mass index was calculated from measured height and weight. Findings: Prevalence of overweight was higher among rural children (25%; P < .001) than children from urban areas (19%) and small cities (17%). Urban children were the least active overall (Cohens' d =−0.4), particularly around lunchtime while at school (d =−0.9 to −1.1). Children from small cities reported the highest levels of physical activity. Conclusions: The results of this study suggest there are rural–urban differences in children's prevalence of overweight and physical activity even within a fairly homogenous Midwestern state.