BACKGROUND: Exercise is effective for musculoskeletal pain. However, physical, social, and environmental factors make it difficult for older adults to persist in exercising. Exergaming is a new pathway that combines exercise with gameplay and may be helpful for older adults to overcome these difficulties and engage in regular exercise. OBJECTIVE: This systematic review aimed to determine the efficacy of exergaming to improve musculoskeletal pain in older adults. METHODS: The search was performed in 5 databases (PubMed, Embase, CINAHL, Web of Science, and Cochrane Library). The risk of bias for randomized controlled studies was assessed using the revised Cochrane Risk of Bias tool in randomized trials (RoB 2), and the methodological quality was assessed using the Physiotherapy Evidence-Based Database scale. Standardized mean difference and 95% CI were calculated using fixed-effects model meta-analyses in the Review Manager version 5.3 (RevMan 5.3). RESULTS: Seven randomized controlled studies were included, which contained 264 older adults. Three of the 7 studies reported significant improvements in pain after the exergaming intervention, but only 1 reported a significant difference between groups after adjustment for baseline (P<.05), and another reported a significant improvement in thermal pain between the 2 groups (P<.001). The results of the meta-analysis of the 7 studies showed no statistically significant improvement in pain compared to the control group (standardized mean difference -0.22; 95% CI -0.47 to 0.02; P=.07). CONCLUSIONS: Although the effects of exergames on musculoskeletal pain in older adults are unknown, exergame training is generally safe, fun, and appealing to older adults. Unsupervised exercise at home is feasible and cost-effective. However, most of the current studies have used commercial exergames, and it is recommended that there should be more cooperation between industries in the future to develop professional rehabilitation exergames that are more suitable for older adults. The sample sizes of the studies included are small, the risk of bias is high, and the results should be interpreted with caution. Further randomized controlled studies with large sample sizes, high quality, and rigor are needed in the future. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42022342325; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=342325.