Understanding the challenges parents of children with disabilities face when seeking to balance work and family is a real concern; however, these challenges have not been well studied. Parents of children with disabilities experience excess challenges in the home domain as a result of their caregiving demands that can lead to challenges in balancing family and work. This is particularly problematic for parents raising children with autism spectrum disorder (ASD). The present study examined the relationship between inter-domain transitions and work-family conflict in order to identify personal and situational factors that were associated with reduced conflict and parenting stress in a population of parents raising children with ASD. Results of this study demonstrated the importance of individuals’ appraisal of transitions on the relationships between inter-domain transitions and work-family conflict and inter-domain transitions and parenting stress. Further, family-supportive supervisor behaviors and segmentation preferences mitigated the experiences of WFC and parenting stress for this population. The results of this study provide important implications for organizations in seeking to help parents of children with ASD more effectively balance their work and family domains.