| Summary: | Meat products have been implicated in many listeriosis outbreaks globally, however there is a dearth of information on the diversity of <i>L. monocytogenes</i> isolates circulating in food products in South Africa. The aim of this study was to investigate the population structure of <i>L. monocytogenes</i> isolated in the meat value chain within the South African market. Based on whole-genome sequence analysis, a total of 217 isolates were classified into two main lineage groupings namely lineages I (<i>n</i> = 97; 44.7%) and II (<i>n</i> = 120; 55.3%). The lineage groups were further differentiated into IIa (<i>n</i> = 95, 43.8%), IVb (<i>n</i> = 69, 31.8%), IIb (<i>n</i> = 28, 12.9%), and IIc (<i>n</i> = 25, 11.5%) sero-groups. The most abundant sequence types (STs) were ST204 (<i>n</i> = 32, 14.7%), ST2 (<i>n</i> = 30, 13.8%), ST1 (<i>n</i> = 25, 11.5%), ST9 (<i>n</i> = 24, 11.1%), and ST321 (<i>n</i> = 21, 9.7%). In addition, 14 clonal complex (CCs) were identified with over-representation of CC1, CC3, and CC121 in “Processed Meat-Beef”, “RTE-Poultry”, and “Raw-Lamb” meat categories, respectively. <i>Listeria</i> pathogenic islands were present in 7.4% (LIPI-1), 21.7% (LIPI-3), and 1.8% (LIPI-4) of the isolates. Mutation leading to premature stop codons was detected in <i>inlA</i> virulence genes across isolates identified as ST121 and ST321. The findings of this study demonstrated a high-level of genomic diversity among <i>L. monocytogenes</i> isolates recovered across the meat value chain control points in South Africa.
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