The international physical inactivity epidemic among children has contributed to child obesity. Schools can be an effective source of physical activity opportunity. A cross-sectional sample of 1306 American children was drawn from the Panel Study of Income Dynamics – Child Development Supplement, 2007. The aim of this study was to determine the role of in-school physical activity on body mass index (BMI) percentile among middle and high school-aged children. Multinomial logistic regression was used to assess the associations between the independent variable, physical activity, and the dependent variable, BMI percentile. After adjusting for covariates, children who had no physical activity during physical education (PE) were much more likely to be obese than normal weight in comparison with those who met the US national requirements (odds ratio = 1.58, confidence interval = 1.14, 2.20). This study suggests that meeting US national guidelines for PE-related physical activity may be effective in preventing obesity.