Severe irritability is a common and clinically important problem longitudinally associated with internalizing and externalizing problems in children. To better understand these mechanisms and to inform treatment research, we tested cognitive-behavioral processes as candidate mediators in the paths from irritability to later problems. Methods: A school sample (N = 238, 48% female, ages 8-10) was assessed at similar to 6-month intervals in fall (T1) and spring (T2) of third to fourth grade, and again the following fall (T3). Measures assessed irritability (T1/predictor); anger and sadness coping, intolerance of uncertainty, and rumination; (T1-T2/mediators); and anxiety, depressive symptoms, reactive aggression, and oppositionality (T1-T3/outcomes). Focused cross-lagged panel models, controlling for gender and grade, were specified to examine full (X-T1 -> M-T2 -> Y-T3) and half (X-T1 -> M-T2;M-T1 -> Y-T2) longitudinal mediation. Across one or more intervals, irritability predicted higher depressive symptoms, anxiety, reactive aggression, oppositionality, intolerance of uncertainty, and poor emotion coping. From T1 irritability to T2/T3 outcomes, mediation was found for poor sadness coping leading to reactive aggression and oppositionality; poor anger coping to anxiety, depressive symptoms, and oppositionality; and intolerance of uncertainty to anxiety. Results offer further evidence for internalizing and externalizing outcomes of youth irritability and new evidence suggesting underlying mechanisms. Irritability may confer risk for externalizing problems via poor sadness/anger coping, and for internalizing problems via poor anger coping and intolerance of uncertainty. Theoretical models and psychosocial treatment should consider addressing regulation of various unpleasant emotions as well as psychological flexibility and tolerating uncertainty.