Key PointsQuestionAre neighborhood and household socioeconomic status associated with children’s brain white matter microstructure and, if so, do obesity and cognitive performance (reflecting environmental stimulation) plausibly mediate the associations?FindingsIn this cross-sectional study of 8842 children who participated in the Adolescent Brain Cognitive Development study, higher neighborhood disadvantage, lower household income, and lower parental educational attainment had independent associations with lower restricted directional diffusion and greater restricted isotropic diffusion in white matter. Greater body mass index and poorer cognitive performance partially explained these associations.MeaningThese findings suggest that future research on children’s brain health may benefit from considering obesity incidence and environmental cognitive enrichment from multiple socioeconomic perspectives.