Although exercise is associated with depression relief, the effects of aerobic exercise (AE) interventions on clinically depressed adult patients have not been clearly supported. The purpose of this meta-analysis was to examine the antidepressant effects of AE versus nonexercise comparators exclusively for depressed adults (18-65 years) recruited through mental health services with a referral or clinical diagnosis of major depression. Eleven e-databases and bibliographies of 19 systematic reviews were searched for relevant randomized controlled clinical trials. A random effects meta-analysis (Hedges' g criterion) was employed for pooling postintervention scores of depression. Heterogeneity and publication bias were examined. Studies were coded considering characteristics of participants and interventions, outcomes and comparisons made, and study design; accordingly, sensitivity and subgroup analyses were calculated. Across 11 eligible trials (13 comparisons) involving 455 patients, AE was delivered on average for 45 min, at moderate intensity, three times/week, for 9.2 weeks and showed a significantly large overall antidepressant effect (g = -0.79, 95% confidence interval = -1.01, -0.57, P < 0.00) with low and nonstatistically significant heterogeneity (I = 21%). No publication bias was found. Sensitivity analyses revealed large or moderate to large antidepressant effects for AE (I ≤ 30%) among trials with lower risk of bias, trials with short-term interventions (up to 4 weeks), and trials involving individual preferences for exercise. Subgroup analyses revealed comparable effects for AE across various settings and delivery formats, and in both outpatients and inpatients regardless symptom severity. Notwithstanding the small number of trials reviewed, AE emerged as an effective antidepressant intervention.