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Millions of nocturnally migrating birds die each year from collisions with built structures, especially brightly illuminated buildings and communication towers. Reducing this source of mortality requires knowledge of important behavioral, meteorological, and anthropogenic factors, yet we lack an understanding of the interacting roles of migration, artificial lighting, and weather conditions in causing fatal bird collisions. Using two decades of collision surveys and concurrent weather and migration measures, we model numbers of collisions occurring at a large urban building in Chicago. We find that the magnitude of nocturnal bird migration, building light output, and wind conditions are the most important predictors of fatal collisions. The greatest mortality occurred when the building was brightly lit during large nocturnal migration events and when winds concentrated birds along the Chicago lakeshore. We estimate that halving lighted window area decreases collision counts by 11× in spring and 6× in fall. Bird mortality could be reduced by ∼60% at this site by decreasing lighted window area to minimum levels historically recorded. Our study provides strong support for a relationship between nocturnal migration magnitude and urban bird mortality, mediated by light pollution and local atmospheric conditions. Although our research focuses on a single site, our findings have global implications for reducing or eliminating a critically important cause of bird mortality.