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Objective: Alliance, Mastery/Self-Efficacy, Problem Actualization, and Problem Clarification exemplify common or nonspecific factors of change in psychotherapy (Grawe, 1997). In this study, we tested the hypothesis that other change factors mediate the alliance–outcome link on a within-person level over the treatment course. Method: Our sample consisted of 193 patients with major depression undergoing intensive inpatient cognitive–behavioral-based therapy. Each week, we assessed depressive symptoms (using the Beck Depression Inventory-II) and change factors during individual therapy. Multilevel mediation models were used to test our hypothesis. Results: As expected, within-person change in Alliance (differentiated into Emotional Bond and Contentment with the Therapist) as well as Mastery/Self-Efficacy and Problem Clarification predicted symptom change over the course of therapy. Moreover, the relation between Contentment with the Therapist and subsequent change in depression was mediated by increased Mastery/Self-Efficacy on a within-person level. Conclusions: Our data suggest that within-person change of alliance and other general change factors precede symptom change in depressive patients, and that the link between alliance and outcome may be partially mediated by enhanced Mastery/Self-Efficacy. Future studies should further elucidate the mechanisms responsible for the alliance–outcome link.