Childhood obesity has been associated with numerous poor health conditions, with geographic disparities demonstrated. Limited research has examined the association between rurality and food security, physical activity, and overweight or obesity among children. We examined rates of food security, physical inactivity, and overweight or obesity among rural and urban children and adolescents, and associations between rurality and these 3 outcomes. We used cross-sectional data from a nationally representative sample of children and adolescents aged 10 to 17 years from the 2019-2020 National Survey of Children's Health (N = 23,199). We calculated frequencies, proportions, and unadjusted associations for each variable by using descriptive statistics and bivariate analyses. We used multivariable logistic regression models to examine the association between rurality and food security, physical activity, and overweight or obesity. After adjusting for sociodemographic factors, rural children and adolescents had higher odds than urban children and adolescents of being overweight or obese (adjusted odds ratio = 1.30; 95% CI, 1.11-1.52); associations between rurality and physical inactivity and food insecurity were not significant. The information from this study is timely for policy makers and community partners to make informed decisions on the allocation of healthy weight and obesity prevention programs for children and adolescents in rural settings. Our study provides information for public health programming and the designing of appropriate dietary and physical activity interventions needed to reduce disparities in obesity prevention among children and adolescents.