Ensuring continuity of care for patients with major depressive disorders poses multiple challenges. We conducted a systematic review and meta-analysis of randomised controlled trials comparing real-time telehealth to face-to-face therapy for individuals with depression. We searched Medline, Embase, and Cochrane Central (to November 2020), conducted a citation analysis (January 2021), and searched clinical trial registries (March 2021). We included randomised controlled trials comparing similar or identical care, delivered via real-time telehealth (phone, video) to face-to-face. Outcomes included: depression severity, quality of life, therapeutic alliance, and care satisfaction. Where data were sufficient, mean differences were calculated. Nine trials (1268 patients) were included. There were no differences between telehealth and face-to-face care for depression severity at post-treatment (SMD -0.04, 95% CI -0.21 to 0.13, p = 0.67) or at other time points, except at 9 months post-treatment (SMD -0.39, 95% CI -0.75 to -0.02, p = 0.04). One trial reported no differences in quality-of-life scores at 3- or 12-months post-treatment. One trial found no differences in therapeutic alliance at weeks 4 and 14 of treatment. There were no differences in treatment satisfaction between telehealth and face-to-face immediately post-treatment (SMD -0.14, 95% CI -0.56 to 0.28, p = 0.51) or at 3 or 12-months. Evidence suggests that for patients with depression or depression symptoms, the provision of care via telehealth may be a viable alternative to the provision of care face-to-face. However, additional trials are needed with longer follow-up, conducted in a wider range of settings, and with younger patients.