The commonalities between anxiety and depression have been discussed before, but few have delineated the potentially different mechanisms through which treatments work for these populations. The current study conducted a comprehensive review of child and adolescent randomized clinical trials that tested cognitive-behavioral therapy (CBT) for anxiety or depression. All studies were required to have assessed both treatment outcomes and at least one theory-specific process target, including behavioral, physiological, cognitive, and coping variables. Using a meta-analytic approach, CBT demonstrated positive treatment gains across anxiety, depression, and general functioning outcomes. CBT for anxiety also produced moderate to large effects across behavioral, physiological, cognitive, and coping processes, with behavioral targets demonstrating potentially the greatest change. CBT for depression produced small effects for cognitive processes but nonsignificant effects for behavioral and coping variables. Findings were generally consistent with CB theory but suggest potentially different mediators in the treatment of anxiety and depression. Results are discussed in terms of implications for mechanisms research, theories of change, and treatment development.