The molecular mechanisms by which pathogenic bacteria alter the structure of intestinal microbial communities are poorly understood. In immunocompetent individuals, Salmonella enterica serotype Typhimurium (S. Typhimurium) causes a self-limiting diarrheal illness, characterized by acute intestinal inflammation that is triggered when the pathogen invades and survives in the intestinal mucosa. S. Typhimurium takes advantage of unique electron acceptors (e.g., tetrathionate and nitrate) and oxygen generated during inflammation to expand its luminal population by respiration. Pathogen expansion leads to the depletion of members of Clostridia that confer many health benefits to the host. The role of type I IFN signaling pathway during intestinal bacterial infection and how this pathway contributes to changes in the luminal environment that result in pathogen expansion remain unknown. Here, we show that STAT2 dependent type I IFN signaling contributes to the establishment of an inflammatory environment by supporting oxygenation of the gut that enables S. Typhimurium to outgrow the resident microbiota. Stat2-/- mice infected with S. Typhimurium exhibit blunted expression of type I IFN stimulated genes in the gut and reduced bacterial burden restricted to the intestinal lumen compared to wild-type mice. Although acute inflammatory pathology was comparable between wild-type and Stat2-/- mice, lower levels of myeloperoxidase accompanied by decreased hypoxia in the gut tissue of Stat2-/- mice were observed. Genetic ablation of the cytochrome bd-II oxidase pathway in S. Typhimurium, which facilitates respiration reduced S. Typhimurium competitiveness. Altogether, our results identify STAT2-mediated inflammation in the gut as a mechanism for pathogen expansion.