INTRODUCTION: The purpose of this systematic review and meta-analysis was to evaluate the effects of exercise on (i) the prevention of cancer-related lymphedema (CRL), and (ii) the treatment of CRL, lymphedema-associated symptoms, and other health outcomes among individuals with CRL. METHODS: An electronic search was undertaken for exercise studies measuring lymphedema and involving individuals at risk of developing or with CRL. The Effective Public Health Practice Project Quality scale was used to assess study quality and overall quality of evidence was assessed using the GRADE approach. Meta-analyses were performed to evaluate effects of exercise on CRL incidence, existing CRL status, lymphedema-associated symptoms and health outcomes. RESULTS: Twelve studies (n = 1,955; 75% moderate-high quality) and 36 studies (n = 1,741; 58% moderate-high quality) were included in the prevention and treatment aim, respectively. Relative risk of developing CRL for those in the exercise group compared with the non-exercise group was 0.90 (95% CI: 0.72, 1.13) overall, and 0.49 (95% CI: 0.28, 0.85) for those with 5 or more lymph nodes removed. For those with CRL in the exercise group, the standardised mean difference (SMD) pre- to post exercise of CRL was -0.11 (95% CI: -0.22, 0.01), and compared with usual care post-intervention the SMD was -0.10 (95% CI: -0.24, 0.04). Improvements post-intervention were observed for pain, upper-body function and strength, lower-body strength, fatigue and quality of life for those in the exercise group (SMD: 0.3-0.8; p < 0.05). CONCLUSIONS: Findings support the application of exercise guidelines for the wider cancer population to those with or at risk of CRL. This includes promotion of aerobic and resistance exercise, and not just resistance exercise alone, as well as unsupervised exercise guided by symptom response.