Objective This study aimed to comprehensively analyze the prevalence， virulence characteristics， and molecular typing of Listeria monocytogenes （L. monocytogenes） isolated from various food sources in Guangxi. By investigating the genetic attributes and potential transmission mechanisms of L. monocytogenes， this research contributes to our understanding of this pathogen.Methods A total of 210 L. monocytogenes strains collected from 2002 to 2020 in Guangxi were subjected to whole genome sequencing （WGS） analysis. The study included the determination of sequence types （STs）， clonal complexes （CC）， and the presence of L. monocytogenes pathogenicity islands （LIPIs）.Results Of the L. monocytogenes isolates， 53.8% were traced back to meat and meat products from 2002 to 2020 in Guangxi. Among these isolates， 59.0% belonged to lineage Ⅱ. The predominant STs were ST8 and ST9. Virulence gene analysis revealed that 79.4% of isolates carried LIPI-1 genes （hly， prfA， plcA， plcB， mpl， and actA）， while 83.7% carried LIPI-2 genes （inlC， inlF， inlJ， and inlK）. Furthermore， 17.6% of isolates carried LIPI-3 genes （llsA， llsB， llsD， llsG， llsH， llsP， llsX， and llsY）.Conclusion Meat and meat products in Guangxi showed the highest prevalence of L. monocytogenes. Molecular typing results demonstrated a high genetic diversity among L. monocytogenes strains. The discriminatory power of WGS makes it a valuable tool for monitoring foodborne listeriosis outbreaks. The distribution of virulence genes indicated that L. monocytogenes of Guangxi had different degree of deletion of virulence genes， underscoring the importance of vigilance regarding highly pathogenic strains that could potentially cause foodborne outbreaks.