This study investigated the associations between the characteristics of adolescents and adults with autism spectrum disorders (ASD) and maternal well-being. Two groups were compared: mothers of adolescents and adults with ASD and co-morbid psychiatric disorders (n = 142) and mothers whose sons or daughters had a single diagnosis of ASD (n = 130). Individuals with co-morbid psychiatric disorders had higher levels of repetitive behaviors, asocial behavior, and unpredictability of behavior than their counterparts with ASD only. They also had poorer rated health as well as more frequent gastrointestinal problems and sleep problems. Mothers of sons and daughters with ASD and co-morbid psychiatric disorders reported higher levels of burden and a poorer quality parent-child relationship than mothers of sons and daughters with ASD only. Higher levels of asocial behavior, unpredictability of behavior, and poorer health in sons and daughters with ASD were predictive of greater burden in mothers and a poorer quality parent-child relationship.