Mothers of children with autism report higher levels of depression than mothers of children with other developmental disabilities. We explored the relations between child characteristics of diagnostic severity and problem behaviors, parenting stress, relationship quality, and depressive symptoms in 70 mothers of young children with autism. We hypothesized that relationship quality and parenting stress would relate to maternal depression beyond contributions of child characteristics. Multiple regression analysis revealed a main effect of parenting stress above and beyond child problem behaviors and autism severity. A significant interaction emerged, with relationship quality buffering the effect of parenting stress on depression. Results suggest that the relation between child problem behaviors and maternal depression should be considered in conjunction with other measures of marriage and family stress. Relationship quality and parenting stress may also represent important factors to be explicitly considered within intervention paradigms for young children with autism spectrum disorders.