Salmonella is ubiquitous bacteria commonly found in the water, animals, humans, and the environment. The transmission is facilitated by human activities, including the irrigation of farm products using contaminated surface water, and is a public health concern. This study was carried out to assess Salmonella contamination in the Ekulu River in the Enugu metropolis and determine their susceptibility to some selected relevant antibiotics. Water samples were collected randomly in the region and processed for isolation and identification of Salmonella spp using the direct plating method. The antimicrobial susceptibility tests of the isolates against ciprofloxacin (5 μg), chloramphenicol (30 μg), amoxicillin (10 μg), and streptomycin (10 μg) were done using the disc-diffusion method. Twenty-six (26) (100 %) of the isolates were resistant to amoxicillin antibiotics, and 42.31 %, 23.07 %, and 46.15 % were resistant to ciprofloxacin, chloramphenicol, and streptomycin, respectively. This study shows the importance of establishing adequate measures to control contamination of surface water used for domestic activities in the Emene community Enugu metropolis. Improved water quality increases health and reduces the transmission of diseases/infections.