Vibrio cholerae is the causative agent of the severe diarrheal disease cholera. Bacteriophages that prey on V. cholerae may be employed as phage therapy against cholera. However, the influence of the chemical environment on the infectivity of vibriophages has been unexplored. Here, we discovered that a common metabolite produced by gut microbeslinear enterobactin (LinEnt), represses vibriophage proliferation. We found that the antiphage effect by LinEnt is due to iron sequestration and that multiple forms of iron sequestration can protect V. cholerae from phage predation. This discovery emphasizes the significance that the chemical environment can have on natural phage infectivity and phage-based interventions.