Disparities in cross-city pandemic severity during the 1918 Influenza Pandemic remain poorly understood. This paper uses newly assembled historical data on annual mortality across 438 U.S. cities to explore the determinants of pandemic mortality. We assess the role of three broad factors: i) pre-pandemic population health and poverty, ii) air pollution, and iii) the timing of onset and proximity to military bases. Using regression analysis, we find that cities in the top tercile of the distribution of pre-pandemic infant mortality had 21 excess deaths per 10,000 residents in 1918 relative to cities in the bottom tercile. Similarly, cities in the top tercile of the distribution of proportion of illiterate residents had 21.3 excess deaths per 10,000 residents during the pandemic relative to cities in the bottom tercile. Cities in the top tercile of the distribution of coal-fired electricity generating capacity, an important source of urban air pollution, had 9.1 excess deaths per 10,000 residents in 1918 relative to cities in the bottom tercile. There was no statistically significant relationship between excess mortality and city proximity to World War I bases or the timing of onset. Together the three statistically significant factors accounted for 50 percent of cross-city variation in excess mortality in 1918.