Background: Health information technologies (HITs) hold enormous promise for improving access to and providing better quality of mental health care. However, despite the spread of such technologies in high-income countries, these technologies have not yet been commonly adopted in low- and middle-income countries. People living in these parts of the world are at risk of experiencing physical, technological, and social health inequalities. A possible solution is to utilize the currently available HITs developed in other counties. Objective: Using participatory design methodologies with Colombian end users (young people, their supportive others, and health professionals), this study aimed to conduct co-design workshops to culturally adapt a Web-based Mental Health eClinic (MHeC) for young people, perform one-on-one user-testing sessions to evaluate an alpha prototype of a Spanish version of the MHeC and adapt it to the Colombian context, and inform the development of a skeletal framework and alpha prototype for a Colombian version of the MHeC (MHeC-C). Methods: This study involved the utilization of a research and development (R&D) cycle including 4 iterative phases: co-design workshops; knowledge translation; tailoring to language, culture, and place (or context); and one-on-one user-testing sessions. Results: A total of 2 co-design workshops were held with 18 users - young people (n=7) and health professionals (n=11). Moreover, 10 users participated in one-on-one user-testing sessions - young people (n=5), supportive others (n=2), and health professionals (n=3). A total of 204 source documents were collected and 605 annotations were coded. A thematic analysis resulted in 6 themes (ie, opinions about the MHeC-C, Colombian context, functionality, content, user interface, and technology platforms). Participants liked the idea of having an MHeC designed and adapted for Colombian young people, and its 5 key elements were acceptable in this context (home page and triage system, self-report assessment, dashboard of results, booking and video-visit system, and personalized well-being plan). However, to be relevant in Colombia, participants stressed the need to develop additional functionality (eg, phone network backup; chat; geolocation; and integration with electronic medical records, apps, or electronic tools) as well as an adaptation of the self-report assessment. Importantly, the latter not only included language but also culture and context. Conclusions: The application of an R&D cycle that also included processes for adaptation to Colombia (language, culture, and context) resulted in the development of an evidence-based, language-appropriate, culturally sensitive, and context-adapted HIT that is relevant, applicable, engaging, and usable in both the short and long term. The resultant R&D cycle allowed for the adaptation of an already available HIT (ie, MHeC) to the MHeC-C - a low-cost and scalable technology solution for low- and middle-income countries like Colombia, which has the potential to provide young people with accessible, available, affordable, and integrated mental health care at the right time.