Mothers’ economic hardship is found to be positively associated with maternal depressive symptoms and depressed mothers are more likely to experience more parenting stress. Research shows that social support might be particularly beneficial for these families, however there are competing views on whether protective factors need to demonstrate direct or moderating effects. Thus, we examined whether the association between income-to-needs and mothers’ parenting stress is mediated via economic pressure and maternal depressive symptoms. Then, we tested the potential protective effect of social support, one model with the main effects and another model with moderating effects. The sample included 3001 mothers from the Future of Families and Child Wellbeing Study. Results demonstrated that the association between income-to-needs ratio and parenting stress was significantly and serially mediated by economic pressure and depressive symptoms. Further, the main effects of social support were significant, however none of the interaction effect of social support were significant. The results suggest that the social support has direct positive effects in decreasing maladaptive outcomes, but it did not buffer earlier experiences of risks. Given the important role social support plays in low-income families with mothers who might be depressed and highly stressed, it can be specifically targeted in prevention and intervention programs.