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BACKGROUND Economic costs of mental disorders for society are huge. Internet-based interventions are often coined as cost-effective alternative to usual care, but evidence is mixed. OBJECTIVE The aim was to review the literature on cost-effectiveness of eHealth interventions for mental disorders compared to usual care and to provide an estimate of the monetary benefits of such interventions compared to usual care. METHODS A systematic review and meta-analysis of (1) randomized controlled trials that (2) included participants with symptoms of mental disorders, (3) investigated a telephone or internet-based intervention, (4) included a control condition in the form of treatment as usual, psychological placebo, waiting list control or bibliotherapy, (5) reported outcomes on both quality of life and costs and (6) were published in English, was conducted. Electronic databases PubMed (including Medline), Embase, Emcare, PsycINFO, Web of Science and The Cochrane Library were searched. Data on risk of bias, quality of the economic evaluation, quality-of-life adjusted life years (QALYs) and costs were extracted from included studies and the incremental net benefit (INB) was calculated and pooled. RESULTS The search yielded 6226 abstracts and 37 studies with 14,946 participants were included. Quality of economic evaluations of included studies was rated to be moderate and risk of bias was high. A random-effects approach was maintained. Analyses suggested internet interventions to be slightly more effective than usual care in terms of QALY gain, Hedges’ g=.052 (95% CI .010; .094, P=.016), and equally expensive, Hedges’ g=.002 (95% CI -.080; 0.84, P=.96). The pooled INB was $255, (95% CI $91; $419, P=.002), favoring eHealth interventions over usual care. Perspective of the economic evaluation and targeted mental disorder moderated results. CONCLUSIONS Findings indicate that cost-effectiveness of e-mental health interventions compared to a care-as-usual approach is likely, but generalizability to new studies is poor given the substantial heterogeneity. This is the first study in the area of mental health to pool cost-effectiveness outcomes in an aggregate-data meta-analysis. CLINICALTRIAL Prospero registration https://www.crd.york.ac.uk/PROSPERO/; registration number: CRD42019141659.