This study investigates the impact of the timing of initial exposure to maternal depression on a comprehensive measure of children's school readiness that incorporates multidimensional developmental domains underlying school adaptation and later success. The Early Development Instrument scores of 59,413 children were linked to their mothers, who were observed from five years before the child's birth to the child's fifth birthday. Exposure to maternal depression was associated with developmental vulnerability in emotional, physical, social, and cognitive domains, and the effects were strongest if the child was first exposed during pregnancy or the preschool period. When controlling for health at birth, health of the child during early childhood, mother's health prior to pregnancy, and the family environment however, the effects of exposure to maternal depression were attenuated. Thus, although maternal depression is a risk factor for children's school readiness, their health and environment compound this effect. A number of different stratifications, variable definitions and robustness checks support the reliability of the findings. The results suggest that mitigating the effects of maternal depression on school readiness is important at any age, and that the programs to address this are likely to lead to improvements far beyond those for maternal depression alone.