Parental stress among parents of children with autism spectrum disorder (ASD) is well-documented in the literature. This study used the mediation model to investigate the relationship between the phenomenon of affiliate stigma and parental stress among parents of children diagnosed with ASD. This cross-sectional study involved 196 parents between 22 and 65 years of age with a child diagnosed with ASD whose age was between 2 and 22 years. The correlations between affiliate stigma, shame, and parental stress were confirmed. Therefore, affiliate stigma was positively associated with shame and parental stress. The results also indicated that the relationship between the phenomenon of affiliate stigma and parental stress is mediated by shame. A practical implication of our findings is that parents of children with ASD participating in stress-reducing interventions should be trained on how to cope with feelings of shame.