Helicobacter pylori, a bacterium known for its association with stomach ulcers, gastritis, and many gastric malignancies. Cytotoxin-associated gene A (cagA) is a polymorphic strain-specific gene that has a role in the pathogenicity of H. pylori, strong relation with the most severe clinical symptoms, and represents a fulcrum for defining H. pylori evolution. In this study, we are presenting a molecular characterization of two pulsotypes of cagA-positive H. pylori samples isolated from gastric biopsies of Egyptian patients living in the Suez Canal region (Ismailia). We investigated the relation between the presence of cagA gene and the prevalence of other virulence genes like vacuolating cytotoxic gene A (vacA), outer inflammatory protein adhesin gene (oipA), and induced by contact with epithelium gene (iceA). Then, we used Pulsed-field gel electrophoresis (PFGE) using XbaI as a restriction enzyme to select the most dominant pulsotypes for performing a whole-genome sequencing (WGS) analysis. We defined the phylogenic relation of our strain with other strains from different geographical locations. Moreover, detailed virulome and resistome information was obtained by using different bioinformatics pipelines. These data represent an additional brick for full characterization of the evolution of H. pylori which in return will help in improving diagnosis and treatment strategies.