Despite evidence documenting activation of the social pain network in response to social rejection and its link to temporary distress, far less is known regarding its role in pervasive emotional difficulties. Moreover, research has not considered the intersection between neural activation to experimentally induced social exclusion and naturally occurring social adversity. This study examined an integrated social pain model of internalizing symptoms, which posits that (i) neural sensitivity in the social pain network is associated with internalizing symptoms, (ii) this linkage is more robust in youth with than without a history of social adversity, and (iii) heightened avoidance motivation serves as one pathway linking neural sensitivity and internalizing symptoms. During a functional magnetic resonance imaging scan, 47 adolescent girls (M age = 15.46 years, SD = .35) with well-characterized histories of peer victimization were exposed to social exclusion. Whole-brain analyses revealed that activation to exclusion in the social pain network was associated with internalizing symptoms. As anticipated, this linkage was stronger in chronically victimized than non-victimized girls and was partially accounted for by avoidance motivation. This research indicates the importance of integrating neural, social and psychological systems of development in efforts to elucidate risk for internalizing symptoms among adolescent girls.