Depression and anxiety are highly prevalent conditions in the United States. Despite the availability of suitable therapeutic options, limited access to high-quality psychiatrists represents a major barrier to treatment. Although telepsychiatry has the potential to improve access to psychiatrists, treatment efficacy in the telepsychiatry model remains unclear. Our primary objective was to determine whether there was a clinically meaningful change in 1 of 2 validated outcome measures of depression and anxiety-the Patient Health Questionnaire-8 (PHQ-8) or the Generalized Anxiety Disorder-7 (GAD-7)-after receiving at least 8 weeks of treatment in an outpatient telepsychiatry setting. We included treatment-seeking patients enrolled in a large outpatient telepsychiatry service that accepts commercial insurance. All analyzed patients completed the GAD-7 and PHQ-8 prior to their first appointment and at least once after 8 weeks of treatment. Treatments included comprehensive diagnostic evaluation, supportive psychotherapy, and medication management. In total, 1826 treatment-seeking patients were evaluated for clinically meaningful changes in GAD-7 and PHQ-8 scores during treatment. Mean treatment duration was 103 (SD 34) days. At baseline, 58.8% (1074/1826) and 60.1% (1097/1826) of patients exhibited at least moderate anxiety and depression, respectively. In response to treatment, mean change for GAD-7 was -6.71 (95% CI -7.03 to -6.40) and for PHQ-8 was -6.85 (95% CI -7.18 to -6.52). Patients with at least moderate symptoms at baseline showed a 45.7% reduction in GAD-7 scores and a 43.1% reduction in PHQ-8 scores. Effect sizes for GAD-7 and PHQ-8, as measured by Cohen d for paired samples, were d=1.30 (P<.001) and d=1.23 (P<.001), respectively. Changes in GAD-7 and PHQ-8 scores correlated with the type of insurance held by the patients. Greatest reductions in scores were observed among patients with commercial insurance (45% and 43.9% reductions in GAD-7 and PHQ-8 scores, respectively). Although patients with Medicare did exhibit statistically significant reductions in GAD-7 and PHQ-8 scores from baseline (P<.001), these improvements were attenuated compared to those in patients with commercial insurance (29.2% and 27.6% reduction in GAD-7 and PHQ-8 scores, respectively). Pairwise comparison tests revealed significant differences in treatment responses in patients with Medicare versus commercial insurance (P<.001). Responses were independent of patient geographic classification (urban vs rural; P=.48 for GAD-7 and P=.07 for PHQ-8). The finding that treatment efficacy was comparable among rural and urban patients indicated that telepsychiatry is a promising approach to overcome treatment disparities that stem from geographical constraints. In this large retrospective data analysis of treatment-seeking patients using a telepsychiatry platform, we found robust and clinically significant improvement in depression and anxiety symptoms during treatment. The results provide further evidence that telepsychiatry is highly effective and has the potential to improve access to psychiatric care.