Background Psychological factors link the co-occurrence of tinnitus-related distress and pain perceptions in patients with chronic tinnitus. Objective This study examines, if treatment-related changes in these factors ameliorate both tinnitus-related distress and pain perceptions in a sample of patients with chronic tinnitus. Methods N = 1238 patients with chronic tinnitus provided pre- and post-treatment ratings of tinnitus-related distress and affective or sensory pain perceptions alongside measures of depressive symptoms and perceived stress. Treatment comprised an intensive tinnitus-specific multimodal treatment program. Using serial indirect-effects analyses, we examined association patterns between baseline values and change rates of those variables that were found to respond to treatment. Results Small effect sizes emerged for changes in tinnitus-related distress, affective (but not sensory) pain perceptions, depressive symptoms, emotional tension and worry. At pre- or post-treatment respectively, baseline values and change rates intercorrelated. Across timepoints, (1) baseline tinnitus-related distress and affective pain perceptions were positively associated with improvements in tinnitus-related distress, affective pain perceptions and depressive symptoms. (2) Baseline depressive symptoms or emotional tension mediated positive associations between baseline tinnitus-related distress and improvement in affective pain perceptions. (3) Change in depressive symptoms mediated the effect of baseline tinnitus-related distress on change in affective pain perceptions-partly through associated change in emotional tension or worry. Mood-independent aspects of emotional tension were negatively associated with improvement in affective pain perceptions. Conclusions Depressive symptoms, emotional tension and worry emerge as key predictors of treatment response and transdiagnostic treatment targets for alleviating tinnitus-related distress and functionally associated affective pain perceptions.