Background Despite the growing number of mental health apps available for smartphones, the perceived usability of these apps from the perspectives of end users or health care experts has rarely been reported. This information is vital, particularly for self-guided mHealth interventions, as perceptions of navigability and quality of content are likely to impact participant engagement and treatment compliance. Objective The aim of this study was to conduct a usability evaluation of a personalized, self-guided, app-based intervention for depression. Methods Participants were administered the System Usability Scale and open-ended questions as part of a semistructured interview. There were 15 participants equally divided into 3 groups: (1) individuals with clinical depression who were the target audience for the app, (2) mental health professionals, and (3) researchers who specialize in the area of eHealth interventions and/or depression research. Results The end-user group rated the app highly, both in quantitative and qualitative assessments. The 2 expert groups highlighted the self-monitoring features and range of established psychological treatment options (such as behavioral activation and cognitive restructuring) but had concerns that the amount and layout of content may be difficult for end users to navigate in a self-directed fashion. The end-user data did not confirm these concerns. Conclusions Encouraging participant engagement via self-monitoring and feedback, as well as personalized messaging, may be a viable way to maintain participation in self-guided interventions. Further evaluation is necessary to determine whether levels of engagement with these features enhance treatment effects.