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Women are more vulnerable to internalizing disorders (e.g., depression and anxiety). This study took an integrative, developmental approach to investigate multidimensional factors associated with the emergence of sex differences in internalizing symptoms, using data from the Adolescent Brain Cognitive Development (ABCD) study. Indices of sex hormone levels (dehydroepiandrosterone, testosterone, and estradiol), physical pubertal development, task-based functional brain activity, family conflict, and internalizing symptoms were drawn from the ABCD study's baseline sample (9- to 10-year-old; N = 11,844). Principal component analysis served as a data-driven dimensionality reduction technique on the internalizing subscales to yield a single robust measure of internalizing symptoms. Moderated mediation analyses assessed whether associations between known risk factors and internalizing symptoms vary by sex. Results revealed direct and indirect effects of physical pubertal development on internalizing symptoms through family conflict across sexes. No effects were found of sex hormone levels or amygdala response to fearful faces on internalizing symptoms. Females did not report overall greater internalizing symptoms relative to males, suggesting that internalizing symptoms have not yet begun to increase in females at this age. Findings provide an essential baseline for future longitudinal research on the endocrine, neurocognitive, and psychosocial factors associated with sex differences in internalizing symptoms.