Helicobacter pylori is a successful etiologic gastric agent that reaches a prevalence around 80% in Colombia. This bacterium is extremely diverse and has shown a phylogeographic pattern. The objective of this study was to perform an analysis of genomic epidemiology of H. pylori in Colombia. We enriched our set of 29 newly sequenced Colombian H. pylori genomes with additional data from public databases, reaching a total of 221 genomes in our dataset. Phylogenetic characterization was carried out using MLST and whole genome SNP analysis. We also performed a characterized the diversity of virulence factors and mutations associated with antimicrobial resistance. Phylogenetic analyzes showed two new Colombian H. pylori clades. Furthermore, many virulence genotype combinations were found, mutations associated with resistance were found for all the studied antibiotics, highlighting 14.4% of the genomes presented profiles associated with resistance to more than one family of antibiotics. Our analyzes described the genomics of Colombian H. pylori and verify the presence of a population group formed exclusively by Colombian isolates. We demonstrated the great diversity among the isolates and that the analysis by comparative genomics of H. pylori are valuable tools to assess the diversity, virulence, and resistance of H. pylori.