Enterohaemorrhagic Escherichia coli (EHEC) O157:H7 is a major cause of gastrointestinal illnesses, particularly among Patients. It is associated with severe complications such as hemorrhagic colitis and hemolytic uremic syndrome (HUS), posing a serious public health threat. Despite its global relevance, there is limited data on the prevalence and molecular characteristics of EHEC O157:H7 in Nigeria. This study investigated the prevalence, virulence profile, and associated risk factors of EHEC O157:H7 among Patients with acute diarrhoea in Tarka and Otukpo Local Government Areas (LGAs) of Benue State, Nigeria. A cross-sectional study was employed involving 400 stool samples collected from Patients presenting with acute diarrhoea at selected hospitals in the study areas. Socio-demographic and environmental data were obtained from caregivers using structured questionnaires. E. coli isolates were cultured. Descriptive statistics and chi-square tests were used to determine prevalence and associations with risk factors. The study identified the high prevalence of E. coli O157:H7 (85.5%) in the stool samples analyzed. While most households had water sources within their premises, a considerable proportion relied on streams (41%) and stored drinking water in wide-mouthed containers (55.8%). Chi-square statistical analysis revealed no significant associations between E. coli O157:H7 prevalence and the assessed risk factors, which included water source, storage methods, sanitation practices (open defecation reported in 20.8% of households), and hygiene habits. Despite the absence of statistically significant associations, the high prevalence of EHEC O157:H7, coupled with inadequate water sources and storage practices, underscores the urgent need for targeted public health interventions. Recommendations include improving sanitation and hygiene education, promoting safe water handling and storage, and implementing continuous surveillance to mitigate the risks associated with EHEC infections in Patients in the region. In addition, the high percentage of isolates with stx1 and stx2 genes indicates a concerning potential for severe disease outcomes.