The Ganga River is a vital freshwater resource supporting millions of people for domestic, agricultural, religious, and industrial purposes. However, increasing urbanization and inadequate wastewater management have led to severe microbial pollution, particularly in major cities such as Kanpur, Uttar Pradesh. The present study assessed faecal contamination and antibiotic resistance patterns among indicator bacteria isolated from the Ganga River along a 20 km urban stretch in Kanpur. Water samples were collected from five strategically selected sites representing varying degrees of anthropogenic influence, including upstream reference, bathing ghats, sewage discharge zones, industrial effluent-affected areas, and downstream locations. Faecal indicator bacteria, namely Escherichia coli, Enterococcus faecalis, and Klebsiella pneumoniae, were isolated using membrane filtration and selective culture techniques. Antibiotic susceptibility testing was carried out using the disc diffusion method against commonly used antibiotics. All sampling sites showed the presence of faecal indicator bacteria, confirming widespread faecal contamination of the river. The highest bacterial densities were recorded at sites receiving direct municipal sewage discharge, while comparatively lower counts were observed at the upstream reference site. Antibiotic resistance was prevalent among all bacterial groups, with high resistance observed against ampicillin, amoxicillin, tetracycline, and cefotaxime. A substantial proportion of isolates exhibited resistance to multiple antibiotics, particularly those recovered from sewage- and industrially impacted sites. Lower resistance levels were recorded for ciprofloxacin and gentamicin.The findings indicate that the Ganga River at Kanpur acts as a reservoir and dissemination pathway for antibiotic-resistant bacteria. Continuous discharge of untreated sewage and antibiotic residues into the river poses significant risks to public health and aquatic ecosystems. The study emphasizes the need for improved wastewater treatment, rational antibiotic usage, and regular monitoring of microbial water quality to mitigate the spread of antibiotic resistance in riverine environments.