The present study examined the impact of autism symptoms and coping strategies on the well-being of mothers of children with autism spectrum disorder (ASD). The sample consisted of 153 mothers of toddlers and 201 mothers of adolescents drawn from two ongoing, longitudinal studies of families of individuals with ASD. For mothers of toddlers, lower levels of emotion-focused coping and higher levels of problem-focused coping were generally associated with better maternal well-being, regardless of the level of child symptomatology. For mothers of adolescents, coping often acted as a buffer when autism symptoms were high. Although there was evidence of maternal distress in both groups, the presence of significant buffering effects reflects adaptation in the face of stress, particularly for mothers of adolescents.