COVID-19 has disrupted everyday life worldwide and is the first disease event since the 1918 H1N1 Spanish influenza (flu) pandemic to demand an urgent global healthcare response. There has been much debate on whether the damage of COVID-19 is due predominantly to the pathogen itself or our response to it. We compare SARS-CoV-2 against three other major pandemics (1347 Black Death, 1520's new world smallpox outbreaks, and 1918 Spanish Flu pandemic) over the course of 700 years to unearth similarities and differences in pathogen, social and medical context, human response and behavior, and long-term social and economic impact that should be used to shape COVID-19 decision-making. We conclude that <100 years ago, pandemic disease events were still largely uncontrolled and unexplained. The extensive damage wreaked by historical pandemics on health, economy, and society was a function of pathogen characteristics and lack of public health resources. Though there remain many similarities in patterns of disease spread and response from 1300 onwards, the major risks posed by COVID-19 arise not from the pathogen, but from indirect effects of control measures on health and core societal activities. Our understanding of the epidemiology and effective treatment of this virus has rapidly improved and attention is shifting toward the identification of long-term control strategies that balance consideration of health in at risk populations, societal behavior, and economic impact. Policymakers should use lessons from previous pandemics to develop appropriate risk assessments and control plans for now-endemic COVID-19, and for future pandemics.