BACKGROUND: Digital mental health interventions (DMHIs), which deliver mental health support via technologies such as mobile apps, can increase access to mental health support, and many studies have demonstrated their effectiveness in improving symptoms. However, user engagement varies, with regard to a user's uptake and sustained interactions with these interventions. OBJECTIVE: This systematic review aims to identify common barriers and facilitators that influence user engagement with DMHIs. METHODS: A systematic search was conducted in the SCOPUS, PubMed, PsycINFO, Web of Science, and Cochrane Library databases. Empirical studies that report qualitative and/or quantitative data were included. RESULTS: A total of 208 articles met the inclusion criteria. The included articles used a variety of methodologies, including interviews, surveys, focus groups, workshops, field studies, and analysis of user reviews. Factors extracted for coding were related to the end user, the program or content offered by the intervention, and the technology and implementation environment. Common barriers included severe mental health issues that hampered engagement, technical issues, and a lack of personalization. Common facilitators were social connectedness facilitated by the intervention, increased insight into health, and a feeling of being in control of one's own health. CONCLUSIONS: Although previous research suggests that DMHIs can be useful in supporting mental health, contextual factors are important determinants of whether users actually engage with these interventions. The factors identified in this review can provide guidance when evaluating DMHIs to help explain and understand user engagement and can inform the design and development of new digital interventions.