Background Mental ill-health is the leading cause of disability worldwide. Moreover, 75% of mental health conditions emerge between the ages of 12 and 25 years. Unfortunately, due to lack of resources and limited engagement with services, a majority of young people affected by mental ill-health do not access evidence-based support. To address this gap, our team has developed a multimodal, scalable digital mental health service (Enhanced Moderated Online Social Therapy [MOST+]) merging real-time, clinician-delivered web chat counseling; interactive user-directed online therapy; expert and peer moderation; and peer-to-peer social networking. Objective The primary aim of this study is to ascertain the feasibility, acceptability, and safety of MOST+. The secondary aims are to assess pre-post changes in clinical, psychosocial, and well-being outcomes and to explore the correlations between system use, perceived helpfulness, and secondary outcome variables. Methods Overall, 157 young people seeking help from a national youth e-mental health service were recruited over 5 weeks. MOST+ was active for 9 weeks. All participants had access to interactive online therapy and integrated web chat counseling. Additional access to peer-to-peer social networking was granted to 73 participants (46.5%) for whom it was deemed safe. The intervention was evaluated via an uncontrolled single-group study. Results Overall, 93 participants completed the follow-up assessment. Most participants had moderate (52/157, 33%) to severe (96/157, 61%) mental health conditions. All a priori feasibility, acceptability, and safety criteria were met. Participants provided mean scores of ≥3.5 (out of 5) on ease of use (mean 3.7, SD 1.1), relevancy (mean 3.9, SD 1.0), helpfulness (mean 3.5, SD 0.9), and overall experience (mean 3.9, SD 0.8). Moreover, 98% (91/93) of participants reported a positive experience using MOST+, 82% (70/93) reported that using MOST+ helped them feel better, 86% (76/93) felt more socially connected using it, and 92% (86/93) said they would recommend it to others. No serious adverse events or inappropriate use were detected, and 97% (90/93) of participants reported feeling safe. There were statistically significant improvements in 8 of the 11 secondary outcomes assessed: psychological distress (d=−0.39; P<.001), perceived stress (d=−0.44; P<.001), psychological well-being (d=0.51; P<.001), depression (d=−0.29; P<.001), loneliness (d=−0.23; P=.04), social support (d=0.30; P<.001), autonomy (d=0.36; P=.001), and self-competence (d=0.30; P<.001). There were significant correlations between system use, perceived helpfulness, and a number of secondary outcome variables. Conclusions MOST+ is a feasible, acceptable, and safe online clinical service for young people with mental ill-health. The high level of perceived helpfulness, the significant improvements in secondary outcomes, and the correlations between indicators of system use and secondary outcome variables provide initial support for the therapeutic potential of MOST+. MOST+ is a promising and scalable platform to deliver standalone e-mental health services as well as enhance the growing international network of face-to-face youth mental health services.