Background: Research has shown varied outcomes for typically-developing (TD) siblings of children with autism spectrum disorder (ASD), suggesting that some emotional and behavioral difficulties may occur only under specific conditions. In addition to characteristics of the children with ASD, family contextual factors may also predict sibling adjustment. Method: This study examined parent marital status and parental stress as moderators of the relation between ASD siblings’ symptom severity and emotional and behavioral adjustment in 56 TD sisters via self- and parent-report. Results: At moderate and high levels of parental stress, TD sisters with siblings with relatively severe ASD symptomatology and with unmarried parents reported the highest levels of emotional and behavioral difficulties. Yet, TD sisters with siblings with relatively less severe ASD symptomatology and with unmarried parents reported the lowest levels of challenging behaviors and emotional symptoms. Conclusions: These findings indicate that clinicians treating families of children with relatively severe ASD and unmarried parents should be particularly cognizant of the functioning of TD sisters.