Higher negative (or lower positive) mood is associated with internalizing and externalizing problems among some, but not all youth, suggesting that contextual factors may influence these temperament-symptom relations. Family conflict also is associated with internalizing and externalizing problems, although it is unclear whether family conflict influences the relation between negative mood and symptoms. To address this gap, we examined whether family conflict moderates the relations between temperamental negative mood and internalizing and externalizing symptoms. Participants were 775 youth (69 % male, 76 % Caucasian). Mothers and youth completed questionnaires when youth were ages 10–12 (time 1) and 12–14 (time 2). When exposed to higher family conflict at time 1, children higher in negative mood experienced higher time 2 internalizing and externalizing problems than children lower in negative mood. When exposed to lower family conflict, children’s internalizing and externalizing symptom levels were similar regardless of their levels of negative mood. Findings suggest that interventions aimed at reducing youth’s risk for internalizing and externalizing symptoms should address conflictual interactions within the larger family system, particularly among youth with higher negative mood.