Chronic wounds present a significant burden to the health care system and the patient. Ozone therapy has been proposed as a treatment for chronic wounds, potentially acting by eliciting mild oxidative stress or disinfection. The purpose of this systematic review is to evaluate the potential benefits and harms of ozone therapy as an advanced care intervention for chronic wounds. Studies were extracted from Google Scholar, PubMed, the Cochrane Library, and reference lists. General inclusion criteria included English-language randomised human trials reporting the use of ozone therapy in the topical treatment of chronic wounds. Primary outcome data included the extent of chronic wound healing, and secondary outcomes included adverse effects. Studies were assessed for level of bias and data quality. Nine studies (n = 453 patients) matched the inclusion criteria and underwent meta-analysis. Overall, there was a significant improvement in wound closure with ozone therapy. Results consistently favour the application of ozone as a treatment for chronic wounds; however, there is no conclusive evidence of ozone therapy as superior compared with standard treatments. Compared with standard care, ozone therapy as an advanced wound care treatment may improve the proportion of chronic wounds healed in a shorter amount of time, but further research is required.