Purpose <p>Parents of children with autism are exposed to stressors associated with the daily care of raising a child with a developmental disability, which may negatively impact parental quality of life (QOL). The specific aim of this study was to examine the relationships between demographic factors, stress, and coping among parental caregivers of children with autism to determine whether predictors of QOL exist.</p> Methods <p>This study was descriptive, and an electronic survey was distributed to parents of children, age 3–21 years old, diagnosed with autism. The survey measured parent-reported demographic factors, severity of the child’s diagnosis of autism, parental stress, coping, and QOL. Data were analyzed using multiple regression.</p> Results <p>Study findings suggest that, in parental caregivers of children with autism in (<i>N</i> = 152) daily stressors, coping self-efficacy, and household income were predictors for physical QOL; daily stressors and coping self-efficacy were predictors of psychological QOL, and coping-self efficacy, household income, and severity of the diagnosis of the child were predictors for environmental QOL.</p> Conclusion <p>Coping self-efficacy and improved income can positively improve QOL, while severity of the diagnosis of autism and daily stressors can negatively impact QOL. Clinically, nurses with a better understanding of the parental stress and coping in parents of children with autism can better recommend tailored resources to improve QOL. Policies to support financial help for families may also improve QOL. Future research should focus on interventions to support caregiver health.</p>