This study tested whether the association between interparental conflict and adolescent externalizing symptoms was moderated by a polygenic composite indexing low dopamine activity (i.e., 7-repeat allele of DRD4; Val alleles of COMT; 10-repeat variants of DAT1) in a sample of seventh-grade adolescents (Mean age = 13.0 years) and their parents. Using a longitudinal, autoregressive design, observational assessments of interparental conflict at Wave 1 predicted increases in a multi-informant measurement of youth externalizing symptoms 2 years later at Wave 3 only for children who were high on the hypodopaminergic composite. Moderation was expressed in a “for better” or “for worse” form hypothesized by differential susceptibility theory. Thus, children high on the dopaminergic composite experienced more externalizing problems than their peers when faced with more destructive conflicts but also fewer externalizing problems when exposed to more constructive interparental conflicts. Mediated moderation findings indicated that adolescent reports of their emotional insecurity in the interparental relationship partially explained the greater genetic susceptibility experienced by these children. More specifically, the dopamine composite moderated the association between Wave 1 interparental conflict and emotional insecurity 1 year later at Wave 2 in the same “for better” or “for worse” pattern as externalizing symptoms. Adolescent insecurity at Wave 2, in turn, predicted their greater externalizing symptoms 1 year later at Wave 3. Post hoc analyses further revealed that the 7-repeat allele of the dopamine receptor D4 (DRD4) gene was the primary source of plasticity in the polygenic composite. Results are discussed as to how they advance process-oriented Gene x Environment models of emotion regulation.