Objective: The objective of the study was to evaluate the effectiveness of telehealth-based exercise intervention on pain, physical function and quality of life in patients with knee osteoarthritis. Design: A systematic review and meta-analysis of randomised controlled trials (RCTs). Methods: Six databases (PubMed, Embase, Cochrane Library, CINAHL, PEDro and Web of Science Core Collection) were searched for relevant randomised controlled trials published from database inception to 3 June 2021. Reviewers independently screened the literature, extracted data and used the Cochrane Collaboration Risk of Bias Tool for quality assessment. A meta-analysis and subgroup analyses, stratified by control condition, intervention duration and delivery type, were conducted by Revman 5.4. The study was reported in compliance with PRISMA statement. Results: A total of 9 independent RCTs with 861 participants were included. The meta-analysis showed that the telehealth-based exercise interventions significantly reduced pain in KOA patients (SMD = −0.28, 95% CI [−0.49, −0.08], p <.01) and produced similar effects to controls in terms of physical function and quality of life. Subgroup analysis revealed that telehealth-based exercise interventions were superior to the use of exercise booklet and usual care in terms of pain and physical function and were similar to face-to-face exercise treatment; a long-term (>3 months) intervention and the use of web and smartphone APPs to deliver exercise interventions were associated with better pain relief and physical function. Conclusions: Telehealth-based exercise intervention is an effective strategy for KOA management during the COVID-19 epidemic, and it is significantly better than usual care in reducing knee pain and improving physical function and was able to achieve the effects of traditional face-to-face exercise treatment. Although the duration and type of delivery associated with the effect of the intervention have been identified, patient preference and acceptability need to be considered in practice.