Introduction: Autism Spectrum Disorder (ASD) is a lifelong neurodevelopmental disorder with mental health impact for parents caring for an autistic child. Despite establishing centers for children with ASD and schools for their special education in Saudi Arabia, there is a lack of studies exploring the impact of ASD on parents. Therefore, a study assessed the impact of caring for a child with ASD on parental stress, emotional well-being, and associated factors in Al-Madinah City. Methods: A cross-sectional study was conducted on parents of children with ASD in schools and Autistic Centers in Al-Madinah City, Saudi Arabia, using the Family Impact Questionnaire (FIQ), Autism Parenting Stress Index (APSI), and the Hospital Anxiety and Depression Scale (HADS) tools. Results: Autism parenting mean stress, depression, and anxiety scores were 1.68± 0.88, 8.50± 4.10 and 10.35± 5.30, respectively. Autistic childrens impact on their parents was significantly positively correlated to parents stress (p<0.001), depression (p<0.001), and anxiety (p<0.001). Parents anxiety was associated with the relationship with their autistic child (p=0.001). There was a significant association between nationality and depression among participants (p=0.032). Post hoc test showed that age of less than 15 years was significantly associated with parental anxiety (p<0.001), depression (p<0.001), and stress (p=0.031), while age of less than 5 years was associated with the impact on a family (p=0.002). Having more than 5 children in the family was associated with parental anxiety (p=0.020), depression (p=0.025), and stress (p=0.032), and motherhood was associated with stress (p<0.001). Lastly, divorce was associated with childs impact on the family (p=0.019). Conclusion: Caring for children with ASD in Saudi Arabia significantly impacts the emotional well-being of parents and siblings, and the impact is influenced by factors such as the childs age, parent-child relationship, nationality, number of children, and marital status. Therefore, comprehensive support and policy initiatives should address this burden and ease the strain on parents caring for autistic children in Saudi Arabia.