Influenza virus causes seasonal outbreaks in temperate regions, with an increase in disease and mortality in the winter months. Dry air combined with cold temperature is known to enable viral transmission. In this study, we asked whether humidity impacts the host response to influenza virus infections. Exposure of mice to low humidity conditions rendered them more susceptible to influenza disease. Mice housed in dry air had impaired mucociliary clearance, innate antiviral defense, and tissue repair function. Moreover, mice exposed to dry air were more susceptible to disease mediated by inflammasome caspases. Our study provides mechanistic insights for the seasonality of the influenza virus epidemics, whereby inhalation of dry air compromises the host’s ability to restrict influenza virus infection.