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Health disparities among children living in poverty underscore the importance of identifying risk and protective factors for childhood obesity. By applying a family stress framework with an equity lens, this study aimed to test the differential associations between maternal distress and child body mass index (BMI) in preschool‐age children living in low‐income families. Pre‐intervention data from an obesity prevention randomized controlled trial were used to assess mother‐reported parental distress and anthropometry collected from children and mothers in a diverse sample of 450 families enrolled in Head Start. Analyses examined associations between maternal distress and child BMI z‐score (BMIz) and moderation by child sex. The sample of children was 49% female, 42% White, 25% Black, 11% Hispanic and 33% had overweight status or obesity. Results indicated higher BMIz for girls compared to boys (β = 0.10, p = 0.03). Child sex modified the association between maternal distress and child BMIz (β = 0.12, p = 0.01). Greater maternal distress was associated with higher BMIz among girls but not boys. Among preschoolers, the maternal distress–BMIz association differed by child sex. Understanding individual differences in how maternal distress relates to childhood obesity may have important implications for obesity prevention efforts. [ABSTRACT FROM AUTHOR]