BACKGROUND: Knee osteoarthritis (OA) presents a significant burden in China due to its high prevalence, aging population, and rising obesity rates. Despite clinical guidelines recommending evidence-based care, limited practitioner training and inadequate telehealth integration hinder effective OA management. OBJECTIVE: The aim of this study was to evaluate the effectiveness of an e-learning program in improving the confidence and knowledge of Chinese physical therapists in managing knee OA and to explore their perceptions of the program. METHODS: This was a randomized controlled trial with 2 parallel arms involving 81 rehabilitation practitioners from 18 Chinese provinces. The intervention group completed a 4-week web-based training program (Physiotherapy Exercise and Physical Activity for Knee Osteoarthritis [PEAK]-Chinese), while the control group received no training. The primary outcome was self-reported confidence in OA management (11-point scale). Secondary outcomes included knowledge (Chinese Knee Osteoarthritis Knowledge Scale [KOAKS]) and likelihood of clinical application of core OA treatments. Process measures and semistructured interviews captured participants' training perceptions. Quantitative data were analyzed using regression models, 2-sided t tests, and descriptive statistics, while thematic analysis was performed on the interview data of 10 participants. RESULTS: A total of 80 participants completed the outcome measures at 4 weeks. The intervention group demonstrated significant improvements in confidence compared to the control group, including managing OA with exercise-based programs (adjusted mean difference=3.27, 95% CI 2.72-3.81), prescribing exercise (adjusted mean difference=3.13, 95% CI 2.55-3.72), and delivering telehealth (adjusted mean difference=4.41, 95% CI 3.77-5.05). KOAKS scores also improved significantly (mean change=9.46); however, certain belief bias related to OA concepts and the use of scans remained unchanged (25/41, 61% and 27/41, 66%, respectively). Approximately 73% (30/41) of the intervention participants rated the course as extremely useful. Interviews emphasized the need for cultural adaptation and practical telehealth training with real-life scenarios to enhance program applicability. CONCLUSIONS: The PEAK program improved Chinese practitioners' confidence and knowledge in managing knee OA, underscoring e-learning's potential to support evidence-based OA care in China. To optimize future implementations, further research strategies could include enhancing cultural relevance, addressing misconceptions, and incorporating practical, real-world training. TRIAL REGISTRATION: Chinese Clinical Trial Register ChiCTR2400091007; https://www.chictr.org.cn/showproj.html?proj=239680.