Infectious diseases are a major source of human mortality and have altered human history. Despite their importance, we lack a thorough understanding of why some historical epidemics were more deadly than others. For many organisms, geographically isolated populations (e.g., populations distant from the mainland) experience more severe epidemics, including after long periods of isolation. These patterns are likely to arise because geographical isolation reduces contact with infectious diseases, causing a corresponding naïvety and susceptibility to those pathogens. Here, we test for equivalent patterns in human populations, but over much longer time frames than have been considered previously.