Background: Global dissemination of the mobilized colistin resistance (mcr) genes provokes a significant public health threat. However, the exact global prevalence of mcr genes, their reservoirs and the potential transmission pathways to humans have not been comprehensively examined. Methods: Bilingual publications in four English (PubMed, Scopus, the Cochrane Database of Systematic Reviews and Web of Science) and two Chinese (CNKI and WANFANG) databases between November 18, 2015 and November 30, 2018 were identified. Systematic review and meta-analysis study were undertaken to examine the prevalence in major reservoirs and propose a potential transmission routes for human infections. Finding: We identified 974 publications, from which 202 observational studies were included in the systematic review and 52 in the meta-analysis. We found 47 mcr-positive countries across six continents with cumulative average 4.6% (0.1-9.3%). Spain, Vietnam and Brazil were the leading prevalent courtiers while China having the most amount mcr-positive bacteria. Pathogenic Escherichia coli (54% of the total) mainly reside in animals (52%), harboring IncI2 (34%). The estimated prevalence of mcr-1 carrying pathogenic E. coli was in decreasing order from food-animals (16.8%, 13.0-20.6%), food (7.1%, 3.4-10.8%), to human (0.7%, 0.5-0.9%), supporting animal-borne food-chain transmission. Carbapenems remain the best choice against human infections caused by mcr-carrying bacteria, except Klebsiella pneumoniae. Interpretation: This study provides a global prevalence of mcr genes by countries, sources, bacteria species, particular bacterial genotype, and plasmid type. We also highlight the potential role of food-chain transmission, and for the first time, suggest rational antimicrobial usage when dealing with mcr-carrying bacterial infections. Funding: Our study was supported by the National Program on Key Research Project of China (2017YFC1600103; 2018YFD0500501; 2018YFD0701001), the Fundamental Research Funds for the Central Universities (2-2050205-18-237), Zhejiang Provincial Natural Science Foundation of China (LR19C180001), Zhejiang University of Hundred Talent Program and National Recruitment Program of Global Youth Experts. Declaration of Interest: We declare no competing interests. Ethical Approval: Not required.