Depression commonly co-occurs with anxiety and externalizing problems. Etiological factors from a central cognitive theory of depression, the Hopelessness Theory (Abramson et al. Psychological Review, 96, 358–372, 1989), were examined to evaluate whether a negative inferential style about cause, consequence, and self interacted with stressors over time to predict prospective elevations in depressive symptoms specifically compared with typically co-occurring symptoms. Negative inferential style was assessed at baseline in a sample of early and middle adolescents (N = 350, sixth to tenth graders). Measures of general depressive, anhedonic depressive, anxious arousal, general internalizing, and externalizing symptoms and occurrence of stressors were assessed at four time points over a 5-month period. Results using hierarchical linear modeling show that a negative inferential style interacted with negative events to predict prospective symptoms of general and anhedonic depression specifically but not anxious arousal, general internalizing or externalizing symptoms. Negative events predicted prospective elevations of symptoms of anxious arousal, internalizing, and externalizing problems.