Objectives Rampant urbanisation rates across the globe demand that we improve our understanding of how infectious diseases spread in modern urban landscapes, where larger and more connected host populations enhance the thriving capacity of certain pathogens. Methods A data-driven approach is employed to study the ability of sexually transmitted diseases (STDs) to thrive in urban areas. The conduciveness of population size of urban areas and their socioeconomic characteristics are used as predictors of disease incidence, using confirmed-case data on STDs in the USA as a case study. Results A superlinear relation between STD incidence and urban population size is found, even after controlling for various socioeconomic aspects, suggesting that doubling the population size of a city results in an expected increase in STD incidence larger than twofold, provided that all other socioeconomic aspects remain fixed. Additionally, the percentage of African-Americans, income inequalities, education and per capita income are found to have a significant impact on the incidence of each of the three STDs studied. Conclusions STDs disproportionately concentrate in larger cities. Hence, larger urban areas merit extra prevention and treatment efforts, especially in lowincome and middle-income countries where urbanisation rates are higher.