BACKGROUND: Addressing antimicrobial resistance (AMR) poses a complex challenge, primarily because of the limited understanding of bacterial antibiotic resistance genes (ARGs) and the spread of these genes across different domains. To bridge this knowledge gap in Ghana, we undertook a comprehensive systematic review and meta-analysis to quantify and estimate the prevalence of circulating ARGs in bacteria isolated from human, animal, and environmental sources. METHODS: A thorough literature search was conducted across three major databases-Web of Science, PubMed, and Scopus-to retrieve all relevant articles related to ARGs in Ghana from the inception of the databases to February 25, 2024. A risk-of-bias evaluation was performed using the Newcastle-Ottawa Scale (NOS), and the data analysis involved descriptive statistics and proportional meta-analysis. RESULTS: Of the 371 articles initially obtained, 38 met the inclusion criteria. These studies adequately covered Ghana geographically. The most prevalent ESBL gene identified was bla CONCLUSION: This review revealed that bacteria obtained from human, animal, and environmental samples in Ghana shared genes associated with AMR. This finding provides evidence on the interconnection of AMR across these three domains. Horizontal gene transfer, which enables the dissemination of ARGs between genetically diverse bacteria, can occur, necessitating a multidisciplinary approach to addressing antimicrobial resistance in Ghana.