The two-factor model of emotion clarifies the complexities of the relationship between anxiety and depression through their varying associations with positive and negative affect. Although this model’s structure has been validated in community samples of children, little research has evaluated the model among clinically referred youth. The present investigation aimed to confirm the two-factor model of emotion within a sample of clinically-referred children (N = 879) and to investigate potential moderators of the model’s relationships within that group. Structural equation modeling demonstrated excellent fit for the two-factor model, and moderating effects for the model structure were found related to age and diagnostic category. These results support the model’s usefulness in describing patterns of psychopathology and temperament for clinically referred children and suggest the potential for a unified treatment approach to internalizing psychopathology.