This study investigated the prevalence and antibiotic resistance of Salmonella species isolated from drinking water sources in Tamale Metropolis. Materials and Methods: Isolation of Salmonella species from 275 different drinking water samples (25 each from dam, well, rain, and bottle, 35 from tap, 40 from water trough, and 100 from sachet) was done using a slightly modified method of the Bacteriological Analytical Manual of the Food and Drugs Administration, USA. 34 Salmonella species isolated from the water samples were examined for their susceptibility to nine different antibiotics using the disc diffusion method. The study was carried out from July 2014 to January 2015. Results: The overall prevalence of Salmonella species was 4.36% (12/275). Dam 16.00% (4/25) and well 16.00% (4/25) water samples were the most contaminated source, followed by rain water (stored) 12.00% (3/25) and tap water samples 2.86% (1/35). There were no significant differences among water samples which were positive for Salmonella species (p>0.05); however, dam and well samples that were positive for Salmonella species differ significantly (p<0.05) from bottle water, sachet water, and water trough samples, which were negative for Salmonella species. The 34 Salmonella isolates were highly resistant to erythromycin (E) (100%) and vancomycin (VA) (94.12%). Few isolates exhibited intermediate resistances to ceftriaxone (CRO) (17.65%), gentamicin (CN) (17.65%), tetracycline (14.71%), chloramphenicol (C) (5.88%), ciprofloxacin (CIP) (2.94%), and amoxicillin (AMC) (2.94%). Salmonella isolates also exhibited six different antibiotic resistant patterns (VA-E, VA-E-AMC, VA-E-CRO, VA-E-C, VA-E-CRO-AMC, and VA-E-AMC-CN). The resistant pattern VA-E (with multiple antibiotic resistance index of 0.22) was the commonest. Conclusion:This study indicated that some drinking water sources for humans and animals in Tamale Metropolis are contaminated with Salmonella species which exhibited varying resistance to various antibiotics. Therefore, consumers of water at the Tamale Metropolis are at risk of Salmonella infection from drinking water from positive water sources in the Tamale Metropolis.