Cholera persists in Ghana due to sanitation challenges. This systematic review aims to synthesize data on the prevalence, antimicrobial resistance, risk factors and community knowledge of cholera in Ghana. Extensive literature searches were conducted in PubMed, Scopus, ScienceDirect, Web of Science and African Journal Online. After screening, we included 33 studies, assessing their quality using the Joanna Briggs Institute checklist. Random effects meta-analysis and subgroup analysis were conducted using RStudio. The pooled prevalence of cholera was 18.42%. Based on subgroups, the highest prevalence was reported in studies that combined rectal swabs and stool samples (57.58%), involved human populations (31.79%) and were conducted in the Greater Accra–Ashanti region (64.52%). Cotrimoxazole had the highest resistance rates (75–100%) and gentamicin the lowest (1–11%). Multidrug resistance ranged between 68% and 100%. There were reports of individual resistance genes to some antibiotics (strA, floR and dfrA1). Case fatality and mortality rates were 3.40% and 2.7%, respectively. Risk factors such as eating street-vended food and proximity to refuse dumps were also reported. Cholera persists in Ghana with high drug resistance rates and regional prevalence variations. Strengthening surveillance, improving sanitation and regulating antibiotics are critical to mitigating outbreaks and resistance spread.