ImportanceAside from widely known cardiovascular implications, higher weight in children may have negative associations with brain microstructure and neurodevelopment.ObjectiveTo evaluate the association of body mass index (BMI) and waist circumference with imaging metrics that approximate brain health.Design, Setting, and ParticipantsThis cross-sectional study used data from the Adolescent Brain Cognitive Development (ABCD) study to examine the association of BMI and waist circumference with multimodal neuroimaging metrics of brain health in cross-sectional and longitudinal analyses over 2 years. From 2016 to 2018, the multicenter ABCD study recruited more than 11 000 demographically representative children aged 9 to 10 years in the US. Children without any history of neurodevelopmental or psychiatric disorders were included in this study, and a subsample of children who completed 2-year follow-up (34%) was included for longitudinal analysis.ExposuresChildren’s weight, height, waist circumference, age, sex, race and ethnicity, socioeconomic status, handedness, puberty status, and magnetic resonance imaging scanner device were retrieved and included in the analysis.Main Outcomes and MeasuresAssociation of preadolescents’ BMI z scores and waist circumference with neuroimaging indicators of brain health: cortical morphometry, resting-state functional connectivity, and white matter microstructure and cytostructure.ResultsA total of 4576 children (2208 [48.3%] female) at a mean (SD) age of 10.0 years (7.6 months) were included in the baseline cross-sectional analysis. There were 609 (13.3%) Black, 925 (20.2%) Hispanic, and 2565 (56.1%) White participants. Of those, 1567 had complete 2-year clinical and imaging information at a mean (SD) age of 12.0 years (7.7 months). In cross-sectional analyses at both time points, higher BMI and waist circumference were associated with lower microstructural integrity and neurite density, most pronounced in the corpus callosum (fractional anisotropy for BMI and waist circumference at baseline and second year: P < .001; neurite density for BMI at baseline: P < .001; neurite density for waist circumference at baseline: P = .09; neurite density for BMI at second year: P = .002; neurite density for waist circumference at second year: P = .05), reduced functional connectivity in reward- and control-related networks (eg, within the salience network for BMI and waist circumference at baseline and second year: P < .002), and thinner brain cortex (eg, for the right rostral middle frontal for BMI and waist circumference at baseline and second year: P < .001). In longitudinal analysis, higher baseline BMI was most strongly associated with decelerated interval development of the prefrontal cortex (left rostral middle frontal: P = .003) and microstructure and cytostructure of the corpus callosum (fractional anisotropy: P = .01; neurite density: P = .02).Conclusions and RelevanceIn this cross-sectional study, higher BMI and waist circumference among children aged 9 to 10 years were associated with imaging metrics of poorer brain structure and connectivity as well as hindered interval development. Future follow-up data from the ABCD study can reveal long-term neurocognitive implications of excess childhood weight. Imaging metrics that had the strongest association with BMI and waist circumference in this population-level analysis may serve as target biomarkers of brain integrity in future treatment trials of childhood obesity.