The potential clinical needs of typically developing (TD) siblings of youth with autism spectrum disorder (ASD) remain disputed. A total of 239 mothers of youth aged 6–17, including one youth with ASD (M = 11.14 years; simplex families) and at least one other youth (M = 11.74 years) completed online standardized measures of various familial factors and TD youth outcomes. Overall, only 6–23% of siblings were identified within the clinical range of emotional, behavioral, or social functioning. Both maternal depression and sibling relationship were identified as key pathways in predicting siblings’ functioning within a good-fitting path analysis model. The current model is presented as a novel base for the development of future research and services for this unique population of children.