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Cognitive-behavioral therapy (CBT) is well supported for treating depressive and anxiety disorders. Trials of CBT for anxiety and depression in primary care have increased over the past decade, yet only one meta-analysis, published in 2015, examined this topic and the scope of that review is relatively narrow. This study conducted a systematic review and meta-analysis of primary care based CBT for depression and anxiety. A search of seven electronic databases, six professional websites, and reference lists from articles meeting inclusion criteria was conducted for studies published between 1900 and November 2018. Fifty-seven eligible studies (including 10,701 participants; 221 effect sizes) of randomized controlled trials were eligible and included for meta-analysis using robust variance estimation in meta-regression. Outcome indicators were depression and anxiety measures. An overall significant treatment effect, d = 0.400, 95% CI (0.235, 0.566), p < 0.001, of CBT for depression and anxiety disorders in primary care was identified. Subgroup analyses indicated significant treatment effect for: (1) depressive (d = 0.425, p < 0.001) and anxiety (d = 0.393, p < 0.01) outcomes, (2) studies conducted inside primary care (d = 0.412, p < 0.001), (3) studies using individual-based CBT (d = 0.412, p < 0.001), (4) studies without primary care physician involvement (d = 0.395, p < 0.001), and (5) studies using both tele-health (d = 0.563, p < 0.001) and in-person CBT (d = 0.363, p < 0.001). The percentage of White participants, treatment composition (CBT only versus CBT + other approaches), and treatment duration were significant moderators. Implications for clinical practice are discussed based on both moderator and subgroup analysis results.