<b><i>Introduction:</i></b> Major depressive disorder (MDD) is a highly prevalent and disabling disorder. This study examines two psychotherapy methods for MDD, behavioral activation (BA), and metacognitive therapy (MCT), when applied as outpatient treatments to severely affected patients. <b><i>Methods:</i></b> The study was conducted in a tertiary outpatient treatment center. Patients with a primary diagnosis of MDD (<i>N</i> = 122) were included in the intention-to-treat sample (55.7% female, mean age 41.9 years). Participants received one individual and one group session weekly for 6 months (M). Assessments took place at baseline, pretreatment, mid-treatment (3 M), post-treatment (6 M), and follow-up (12 M). The primary outcome was depressive symptomatology assessed by the Hamilton Rating Scale for Depression at 12 M follow-up. Secondary outcomes included general symptom severity, psychosocial functioning, and quality of life. <b><i>Results:</i></b> Linear mixed models indicated a change in depressive symptoms (<i>F</i>(2, 83.495) = 12.253, <i>p</i> < 0.001) but no between-group effect (<i>F</i>(1, 97.352) = 0.183, <i>p</i> = 0.670). Within-group effect sizes were medium for MCT (post-treatment: <i>d</i> = 0.610; follow-up: <i>d</i> = 0.692) and small to medium for BA (post-treatment: <i>d</i> = 0.636, follow-up: <i>d</i> = 0.326). In secondary outcomes, there were improvements (<i>p</i> ≤ 0.040) with medium to large within-group effect sizes (<i>d</i> ≥ 0.501) but no between-group effects (<i>p</i> ≥ 0.304). Response and remission rates did not differ between conditions at follow-up (response MCT: 12.9%, BA: 13.3%, remission MCT: 9.7%, BA: 10.0%). The deterioration rate was lower in MCT than in BA (χ<sup>2</sup><sub>1</sub> = 5.466, <i>p</i> = 0.019, NTT = 7.4). <b><i>Discussion:</i></b> Both MCT and BA showed symptom reductions. Remission and response rates were lower than in previous studies, highlighting the need for further improvements in adapting/implementing treatments for severely affected patients with MDD.