Gastric cancer is the fourth-leading cause of cancer death worldwide. About 80% of cases are attributable to infection with the bacterium Helicobacter pylori (Hp). Untreated Hp infection causes lifelong stomach inflammation that does not eradicate the bacterium. In some individuals, stomach inflammation leads to preneoplastic progression, a series of sequential tissue changes including loss of gastric acid-producing parietal cells, metaplasia, dysplasia, and finally cancer. Whether and how Hp infection and associated inflammation can promote each stage of disease development is not well understood. In a mouse model, induction of a constitutively active Kras allele in the stomach recapitulates the same gastric preneoplastic progression seen in humans (loss of parietal cells followed by development of metaplasia and dysplasia). Sustained Hp infection plus active KRAS expression (Hp+KRAS+) led to greater immunopathology, altered T cell and macrophage polarization, increased cell proliferation, altered metaplasia marker expression, and accelerated dysplasia, compared to Hp-KRAS+ mice. These findings suggest that gastric inflammation and disease progression may differ between Hp+ vs. Hp– cases, which could have important therapeutic implications in humans.