Although evidence suggests that neighborhood context, particularly socioeconomic context, influences child obesity, little is known about how these neighborhood factors may be heterogeneous rather than monolithic. Using a novel dataset comprised of the electronic medical records for over 250,000 children aged 2–17 nested within 992 neighborhoods in the greater Houston area, we assessed whether neighborhoods influenced the obesity of children differently based on sex. Results indicated that neighborhood disadvantage, assessed using a comprehensive, multidimensional, latent profile analysis-generated measure, had a strong, positive association with the odds of obesity for both boys and girls. Interactions revealed that the relationship between disadvantage and obesity was stronger for girls, relative to boys. Our findings demonstrated the complex dynamics underlying the influence of residential neighborhood context on obesity for specific subgroups of children. •We identify how, for whom, and when neighborhoods matter for childhood obesity.•Children in the most disadvantaged neighborhoods have greater odds of obesity.•Girls are more vulnerable to neighborhoods than boys throughout childhood.•As neighborhood disadvantage increases, the influence is greater for girls.•Complex dynamics underlie the influence of neighborhoods on child obesity.