In the first half of the twentieth century, the rate of death from infectious disease in the United States fell precipitously. Although this decline is well-known and well-documented, there is surprisingly little evidence about whether it took place uniformly across the regions of the United States. We use data on infectious disease deaths from all reporting U.S. cities to describe regional patterns in the decline of urban infectious mortality from 1900 to 1948. We report three main results. First, urban infectious mortality was higher in the South in every year from 1900 to 1948. Second, infectious mortality declined later in southern cities than in cities in the other regions. Third, comparatively high infectious mortality in southern cities was driven primarily by extremely high infectious mortality among African Americans. From 1906 to 1920, African Americans in cities experienced a rate of death from infectious disease that was greater than what urban whites experienced during the 1918 flu pandemic.