Background: Depression has a high prevalence among young adults, especially during the COVID-19 pandemic. However, mental health services remain scarce and underutilized worldwide. Mental health chatbots are a novel digital technology to provide fully automated interventions for depressive symptoms. Objective: The purpose of this study was to test the clinical effectiveness and nonclinical performance of a cognitive behavioral therapy (CBT)–based mental health chatbot (XiaoE) for young adults with depressive symptoms during the COVID-19 pandemic. Methods: In a single-blind, 3-arm randomized controlled trial, participants manifesting depressive symptoms recruited from a Chinese university were randomly assigned to a mental health chatbot (XiaoE; n=49), an e-book (n=49), or a general chatbot (Xiaoai; n=50) group in a ratio of 1:1:1. Participants received a 1-week intervention. The primary outcome was the reduction of depressive symptoms according to the 9-item Patient Health Questionnaire (PHQ-9) at 1 week later (T1) and 1 month later (T2). Both intention-to-treat and per-protocol analyses were conducted under analysis of covariance models adjusting for baseline data. Controlled multiple imputation and δ-based sensitivity analysis were performed for missing data. The secondary outcomes were the level of working alliance measured using the Working Alliance Questionnaire (WAQ), usability measured using the Usability Metric for User Experience-LITE (UMUX-LITE), and acceptability measured using the Acceptability Scale (AS). Results: Participants were on average 18.78 years old, and 37.2% (55/148) were female. The mean baseline PHQ-9 score was 10.02 (SD 3.18; range 2-19). Intention-to-treat analysis revealed lower PHQ-9 scores among participants in the XiaoE group compared with participants in the e-book group and Xiaoai group at both T1 (F2,136=17.011; P<.001; d=0.51) and T2 (F2,136=5.477; P=.005; d=0.31). Better working alliance (WAQ; F2,145=3.407; P=.04) and acceptability (AS; F2,145=4.322; P=.02) were discovered with XiaoE, while no significant difference among arms was found for usability (UMUX-LITE; F2,145=0.968; P=.38). Conclusions: A CBT-based chatbot is a feasible and engaging digital therapeutic approach that allows easy accessibility and self-guided mental health assistance for young adults with depressive symptoms. A systematic evaluation of nonclinical metrics for a mental health chatbot has been established in this study. In the future, focus on both clinical outcomes and nonclinical metrics is necessary to explore the mechanism by which mental health chatbots work on patients. Further evidence is required to confirm the long-term effectiveness of the mental health chatbot via trails replicated with a longer dose, as well as exploration of its stronger efficacy in comparison with other active controls. Trial Registration: Chinese Clinical Trial Registry ChiCTR2100052532; http://www.chictr.org.cn/showproj.aspx?proj=135744