Background: Some studies have suggested that siblings of children with chronic disorders display higher empathy and more prosocial behavior than typically developing (TD) children. However, the evidence with regards to siblings of children with Autism Spectrum Disorder (ASD) is mixed. Studies have shown that siblings of children with ASD are at higher risk than TD children of psychosocial impairments, including lower social functioning and social cognitive deficits. The first aim of the current study was to compare the prosocial behavior of siblings of children with ASD to siblings of children with physical disabilities and TD children. The second aim was to investigate intra- and interpersonal predictors of prosocial behavior among siblings of children with ASD. Method: The dataset was drawn from baseline data in the SIBS project, a project investigating the feasibility and effectiveness of a group intervention for siblings and parents of children with chronic disorders. In the current study, three groups were included; (1) siblings of children with ASD (n = 47), (2) siblings of children with physical disabilities (n = 42), and (3) TD controls (n = 44). Siblings prosocial behavior and mental health were assessed with the Strengths and Difficulties Questionnaire, siblings’ adaptation to their brother’s or sister’s disorder was assessed with the Negative Adjustment Scale, and parent-child communication was assessed with the Parent-Child Communication Scale. Results: There were no significant differences between siblings of children with ASD and siblings of children with physical disabilities or TD controls in prosocial behavior. Siblings’ mental health, negative adaptation, and parent-child communication explained 25% of the variance in father-reported prosocial behavior among siblings of children with ASD. However, only siblings’ externalizing difficulties was a significant predictor. Conclusion: Siblings of children with ASD display normative levels of prosocial behavior. Intra- and interpersonal variables have little impact on prosocial behavior among siblings of children with ASD.