Multidrug resistance and invasiveness of non-typhoidal Salmonella (NTS) serovars have in recent times brought to the fore the public health risk associated with salmonellosis. This study was aimed at profiling NTS serovars isolated from food animals and humans for their susceptibility to antibiotics and plasmid replicon types. Forty seven NTS serovars were profiled for their susceptibility to antibiotics using the disk diffusion method. Polymerase chain reaction based replicon typing assay was used for profiling plasmid replicon types detected in Salmonella isolates. High rate of resistance were found for amoxicillin/clavulanic acid (40/47; 85.1%), cefuroxime (38/47; 80.9%) and ceftazidime (30/47; 63.8%). Thirty one (65.9%) and 33 (70.2%) showed intermediate resistance to ofloxacin and ciprofloxacin respectively. Plasmids of sizes ranging from 14.3 to 16.7 kb were detected in 24 (51.1%) of Salmonella isolates with some serovars harbouring multiple plasmids. FIA, FIB, Frep and W plasmid replicon types were detected in 11, 4, 2 and 1 of the Salmonella isolates respectively. Three of the isolates harboured both FIA and FIB replicon types. The high rate of resistance to β-lactams observed in Salmonella serovars harbouring different plasmid replicon types in this study highlight potential public health threat and the need for prudent use of antibiotics in human and veterinary medicine.