In the centuries following Christopher Columbus’s 1492 journey to the Americas, transoceanic voyages opened unprecedented pathways for global pathogen circulation. Yet no biological transfer is a single, discrete event. We use mathematical modeling to quantify historical risk of shipborne pathogen introduction, exploring the respective contributions of journey time, ship size, population susceptibility, transmission intensity, density dependence, and pathogen biology. We contextualize our results using port arrivals data from San Francisco, 1850–1852, and from a selection of historically significant voyages, 1492–1918. We offer numerical estimates of introduction risk across historically-realistic journey times and ship population sizes, and show that steam travel and shipping regimes that involved frequent, large-scale movement of people both substantially increased risk of transoceanic pathogen circulation.