Social-emotional behavior in autism spectrum disorder (ASD) was examined among high-risk (HR; siblings of children diagnosed with ASD) and low-risk (LR; no family history of ASD) toddlers. Caregivers completed the Infant-Toddler Social Emotional Assessment (ITSEA) at 18 months, and blind diagnostic assessment for ASD was conducted at 36 months. Results indicated impairment in social-emotional functioning among HR toddlers subsequently diagnosed with ASD compared to other HR and LR toddlers, such that ITSEA domains (Internalizing, Dysregulation, Competence) and subdomains predicted later ASD symptoms and diagnosis. Receiver operating curves of optimal ITSEA cutoffs ranged from 0.23 to 0.44 for sensitivity, and 0.74 to 0.89 for specificity. Although classification accuracy for ASD was limited, group differences highlight the importance of considering social-emotional development when assessing ASD risk.