The present study examines the efficacy of Positive Psychotherapy (PPT) on psychological well-being, happiness, and satisfaction with life. We investigated people suffering from different kinds of depressive disorders, comparing it to Cognitive Behavioral Therapy (CBT). PPT is an empirically validated intervention targeting positive resources and personal strengths. It aims at amplifying well-being while also ameliorating the impact of symptoms. In a controlled two-center-study, we randomly assigned 92 out-patient participants with a DSM-IV diagnosis of major depressive disorder and/or Dysthymia to 14 sessions of manualized PPT or CBT group therapy. We assessed outcomes related to well-being using the Flourishing Scale, the Satisfaction with Life Scale, and the Positive Psychotherapy Inventory (PPTI). The PPTI represents the five components of Seligman’s PERMA-model of flourishing, encompassing positive emotions, engagement, positive relationships, meaning, and accomplishment. We took measurements before and after the intervention, and at a 6-months follow-up. Moreover, we considered a list of moderators that may impact the efficacy of PPT. PPT resulted in significant improvements in all measures, and these improvements remained stable for up to 6 months. Using 2 × 2 mixed-effects models (T1 vs. T2), we found significant interactions for all three main scales and two out of the five PPTI subscales. These interactions depicted significantly better outcomes for PPT at post-treatment. Regarding the follow-up (T1 vs. T3), we did not find significant interactions, and thus, there were no differences between the two therapies. No demographics or characteristics of the treatments were significant moderators. Summarized, these findings provide support for the effectiveness of PPT in increasing happiness, well-being, and quality of life. We can confirm that PPT is an additional tool for the enhancement of positive mental health.