Early life stress (ELS) has been implicated in the development of aggression, though the exact mechanisms remain unknown. This study tested associations between ELS, callousness, and stress reactivity in the prediction of school-age and persistent early childhood aggression. A longitudinal sample of 185 mother–child dyads completed a lab visit and mothers completed an online follow-up when children were preschool-aged and school-aged, respectively. Physiological and behavioral measures of stress reactivity were collected during the preschool period. Ratings of child aggressive behavior, ELS, and callousness were collected as well. The results suggested that ELS was related to measures of both school-age and persistent early childhood aggression, and that callousness had a mediating role in this process. Cortisol reactivity also moderated the association between ELS and persistent childhood aggression, such that the ELS–aggression relationship was stronger among children who had higher levels of cortisol reactivity during the preschool period. Clinical implications are discussed.