Inter-limb asymmetry in lower-limb functional performance has been associated with increased risk of sport injury; however, findings are not always consistent. To conduct a systematic review on whether inter-limb asymmetry in lower-limb functional performance can predict sport injury. Four electronic databases (MEDLINE, EMBASE, Web of Science, and SportDiscus) were systematically searched for prospective cohort studies reporting the association between inter-limb asymmetry in lower-limb functional performance and sport injury. A total of 28 prospective cohort studies were included in the analyses. Collectively, the findings were highly inconsistent, and a clear statement on the association between each asymmetry and sport injury was difficult. Highly inconsistent findings make it difficult to create clear recommendations on the relationship between the inter-limb asymmetry in lower-limb functional performance (power, muscle flexibility, and dynamic balance) and sport injury. The influence of potential factors (selection of tests/parameters, participant characteristics, definition of injury, and ways of calculating asymmetry) should be considered when using previous findings.