BackgroundBehavioral activation is an effective treatment for reducing depression. As depressive disorders affect many people worldwide, internet-based behavioral activation (iBA) could provide enhanced treatment access.ObjectiveThis study aimed to investigate whether iBA is effective in reducing depressive symptoms and to assess the impact on secondary outcomes.MethodsWe systematically searched MEDLINE, PsycINFO, PSYNDEX, and CENTRAL up to December 2021 for eligible randomized controlled trials. In addition, a reference search was conducted. Title and abstract screening, as well as a full-text screening, was conducted by 2 independent reviewers. Randomized controlled trials that investigated the effectiveness of iBA for depression as a treatment or main component were included. Randomized controlled trials had to report depressive symptoms, with a quantitative outcome measure and assess an adult population with depressive symptoms above cutoff. Two independent reviewers performed the data extraction and risk of bias assessment. Data were pooled in random-effects meta-analyses. The primary outcome was self-reported depressive symptoms posttreatment. This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines.ResultsA total of 12 randomized controlled trials, with 3274 participants (88% female, 43.61 years) were included. iBA was more effective in reducing depressive symptom severity posttreatment than inactive control groups (standardized mean difference −0.49; 95% CI −0.63 to −0.34;P<.001). The overall level of heterogeneity was moderate to substantial (I2=53%). No significant effect of iBA on depressive symptoms could be found at 6-month follow-up. Participants assigned to iBA also experienced a significant reduction of anxiety and a significant increase in quality of life and activation compared to the inactive control groups. The results remained robust in multiple sensitivity analyses. The risk of bias assessment revealed at least some concerns for all studies, and there was evidence of slight publication bias.ConclusionsThis systematic review and meta-analysis implies that iBA is effective in reducing depressive symptoms. It represents a promising treatment option, providing treatment access where no treatment is available yet.Trial RegistrationInternational Prospective Register of Systematic Reviews CRD42021236822; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=236822