Wastewater use for crop irrigation and aquaculture is commonly practiced by communities situated close to wastewater treatment ponds. The objective of this study was to characterize Salmonella spp. and their antimicrobial susceptibility patterns among isolates from wastewater and Tilapia fish. A total of 123 Salmonella spp. isolates were isolated from 52 water and 21 fish intestinal samples. Genotyping of Salmonella spp. isolates was done by Pulsed-field Gel Electrophoresis (PFGE). Antimicrobial susceptibility testing was done by the minimal inhibitory concentration (MIC) technique. A total of 123 Salmonella spp. isolates represented 13 different serovars and 22 PFGE groups. Salmonella serovars showed resistance to 8 out of 14 antimicrobials; sulfamethaxazole (94%), streptomycin (61%), tetracycline (22%), ciprofloxacin and nalidixic acid (17%), trimethoprim (11%); gentamycin and chloramphenicol (6%). Salmonella Kentucky, S. Chandans, S. Durban and S. Kiambu showed multiple antimicrobial resistance to 7, 6 and 3 antimicrobials, respectively. This study has demonstrated that wastewater at the study sites is contaminated with Salmonella spp. which are resistant to common antimicrobials used for treatment of diseases in humans. Wastewater may, therefore, contaminate pristine surface water bodies and foodstuffs including fish and irrigated crops as well as food handlers.