Maternal depression has consistently demonstrated reliability as a predictor of major depression in children. However, the effect of gender as a potential moderator remains under-researched. This study examined gender differences in depression and hypothesized that maternal depression would be more greatly associated with depression in girls by early adolescence. A representative sample of 7237 participants from the Growing Up in Ireland national longitudinal study of Irish children was examined across two waves when participants were aged 9 and 13. Separate multiple regression analyses were run for girls and boys to ascertain if maternal depression and other key variables predicted child depression by age 13. A third analysis looked at the effect of gender. Maternal depression when the children were aged 9 was found predictive of depressive symptomology by age 13 in girls but not for boys. Additionally, conflict with caregivers, household income, and bullying were significant predictors for both genders. Gender significantly predicted youth depression when the child was female (R[superscript 2] = 0.13, ƒ[superscript 2] = 0.25). These findings indicate that late childhood to early adolescence is a vulnerable period for girls during which they appear more susceptible to developing depressive symptomology than boys, particularly when exposed to maternal depression.