We investigated the relationship between neighborhood disadvantage (area deprivation index [ADI]) and intracortical myelination (T1-weighted/T2-weighted ratio at deep to superficial cortical levels), and the potential mediating role of the body mass index (BMI) and perceived stress in 92 adults. Worse ADI was correlated with increased BMI and perceived stress (p's<.05). Non-rotated partial least squares analysis revealed associations between worse ADI and decreased myelination in middle/deep cortex in supramarginal, temporal, and primary motor regions and increased myelination in superficial cortex in medial prefrontal and cingulate regions (p<.001); thus, neighborhood disadvantage may influence the flexibility of information processing involved in reward, emotion regulation, and cognition. Structural equation modelling revealed increased BMI as partially mediating the relationship between worse ADI and observed myelination increases (p=.02). Further, trans-fatty acid intake was correlated with observed myelination increases (p=.03), suggesting the importance of dietary quality. These data further suggest ramifications of neighborhood disadvantage on brain health.