<p>The long-standing debate regarding the association between family adversity, irritability, and psychopathology centers on whether it manifests in a domain-general or domain-specific manner. This study seeks to advance the discussion by examining the direct and indirect effects of irritability on the associations between family adversity and psychopathology, with particular attention to individual differences in irritability susceptibility. Data was drawn from a longitudinal study (<i>N</i> = 4,313; 50.3% girl; <i>M</i>age = 13.17, <i>SD</i> = 1.81), in which irritability, psychopathology, and family adversity were assessed by questionnaires. Adolescents manifested in both domain-general and partially domain-specific ways: some adolescents exhibited both externalizing and internalizing psychopathology under the influence of phasic and tonic irritability, while others displayed externalizing psychopathology specifically associated with phasic irritability, or internalizing psychopathology specifically linked to tonic irritability. Furthermore, family adversity was associated with psychopathology both through a common irritability pathway and specific pathways where particular types of adversity affected specific psychopathology via distinct irritability dimensions. This study provides a preliminary map of the domain-general and domain-specific pathways linking family adversity, irritability, and psychopathology, thereby offering a framework to guide targeted interventions aimed at preventing the progression to externalizing or internalizing psychopathology.</p>