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In this work, we analysed human isolates of nontyphoidal <i>Salmonella enterica</i> subsp. <i>enterica</i> (NTS), which were collected from salmonellosis cases in Armenia from 1996 to 2019. This disease became a leading food-borne bacterial infection in the region, with the younger age groups especially affected. The isolates were characterised by serotyping, Enterobacterial Repetitive Intergenic Consensus (ERIC-PCR) typing, and whole genome sequencing (WGS). The main serotypes were <i>S</i>. Typhimurium, <i>S</i>. Enteritidis, and <i>S</i>. Arizonae. ERIC-PCR indicated a high degree of clonality among <i>S</i>. Typhimurium strains, which were also multidrug-resistant and produced extended spectrum beta-lactamases. During the study period, the frequency of <i>S</i>. Typhimurium and <i>S</i>. Arizonae isolations decreased, but with the increase in <i>S</i>. Enteritidis and other NTS. A total of 42 NTS isolates were subjected to WGS and explored for virulence-related traits and the corresponding genetic elements. Some virulence and genetic factors were shared by all NTS serotypes, while the main differences were attributed to the serotype-specific diversity of virulence genes, SPIs, virulence plasmids, and phages. The results indicated the variability and dynamics in the epidemiology of salmonellosis and a high virulence potential of human NTS isolates circulating in the region.