We evaluated autism spectrum disorder (ASD) characteristics and social behavior in Angelman (AS; n = 19; mean age = 10.35 years), Cornelia de Lange (CdLS; n = 15; mean age = 12.40 years), and Cri du Chat (CdCS, also known as 5 p-syndrome; n = 19; mean age = 8.80 years) syndromes. The proportion of individuals meeting the ASD cutoff on the Social Communication Questionnaire was significantly higher in the AS and CdLS groups than in the CdCS group (p < .01). The groups demonstrated divergent social behavior profiles during social conditions in which adult availability, adult familiarity, and social demand were manipulated. Social enjoyment was significantly heightened in AS, whereas social approaches were heightened in individuals with CdCS. Social motivation, social communication, and enjoyment were significantly lower in CdLS. The findings highlight the importance of detailed observation when evaluating ASD and social behavior in genetic syndromes.