Objective <p>The aim of this systematic review and meta-analysis was to investigate the association between physical activity levels and the risk of developing new-onset chronic kidney disease (CKD).</p> Methods <p>In accordance with PRISMA guidelines and PROSPERO registration, a detailed literature search was conducted in PubMed, Embase, Scopus, Cochrane and Web of Science databases until April 13, 2025. Meta-analysis was performed using random effect model, assessing heterogeneity and publication bias.</p> Results <p>Thirteen prospective cohort studies were included, with a pooled analysis showing a protective effect of low and moderate physical activity against CKD (hazard ratio= 0.91; 95% CI: 0.87–0.96). High levels of physical activity showed a stronger preventive effect (hazard ratio= 0.85; 95% CI: 0.79–0.92). The quality assessment of the studies indicates acceptable quality, with good results for selection and outcomes, but some shortcomings in comparability. No publication bias was found for either outcome.</p> Conclusion <p>The results of this study provide compelling evidence that physical activity, particularly at higher levels, significantly reduces the risk of new-onset CKD and alsoemphasize the importance of incorporating physical activity into public health strategies aimed at preventing chronic kidney disease. Given the stronger preventive effect observed with high levels of physical activity, the promotion and encouragement of individuals should be emphasized. However, heterogeneity in study designs and definitions of physical activity and CKD may limit the generalizability of these findings</p>