The pervasiveness of influenza among humans and its rapid spread during pandemics create a false sense that all humans are affected equally. In this work, we show that neighborhood-level social determinants were associated with greater burdens of pandemic influenza in 1918 and several other diseases in a major US city. We show that literacy, homeownership, and unemployment were associated with cumulative influenza mortality as well as measures of the speed of transmission using a unique dataset describing the home location and week of death of individuals who died during the influenza pandemic in 1918. Our results suggest that, similar to other infectious diseases, social disparities should be a focus of research and public health response in future pandemics.