The primary objectives of the current prospective longitudinal study were to (a) describe social functioning outcomes and (b) identify childhood predictors of social functioning in young adults with (22q11.2DS). Childhood predictors of young adult social functioning were examined. Family environment and parental stress in adolescence were investigated as potential mediators between childhood variables and adult social functioning. Parent rated childhood internalizing symptoms significantly predicted young adult social functioning in 22q11.2DS, even after controlling for concurrent positive symptoms of psychosis, and problem behaviors contributing to parenting stress in adolescence partially mediated this relationship. These findings highlight child internalizing symptoms and adolescent problem behaviors as potential targets for social functioning interventions in 22q11.2DS.