Flood hydrologic response is influenced by rainfall structure (i.e., variability in space and time). How this structure shapes flood frequency is unknown, and flood frequency analyses typically neglect or simplify potentially important aspects of rainfall variability. This study seeks to understand how rainfall structure impacts flood frequency. We use stochastic storm transposition combined with a 15‐year record of hourly, 4‐km2 radar rainfall to generate 10,000 synthetic extreme rain events. These events are resampled into four “scenarios” with differing spatial and temporal resolutions, which are used as input to a distributed hydrologic model. Analysis of variance is used to identify the proportions of total flood peak variability attributable to spatial and to temporal rainfall variability under two antecedent soil moisture conditions. We simulate peak discharges for recurrence intervals of 2 to 500 years for 1,343 subwatersheds ranging in size from 16 to 4,400 km2 in Turkey River in the Midwestern United States, which is situated in a typically humid continental climactic region. Antecedent soil moisture modulates the role of rainfall structure in simulated flood response, particularly for more frequent events and large watershed scales. Rainfall spatial structure is more important than temporal structure for drainage areas larger than approximately 2,000 km2 (approximately 200 km2) for wet (dry) initial soil conditions, especially when soils are dry, while the reverse is true for smaller subwatersheds. The results appear to be related to the differing propensities for surface and subsurface runoff production as a function of basin scale, event magnitude, and soil saturation. Our results suggest that hydrologic model‐based flood frequency analyses, and particularly efforts attempting to spanning a range of scales, must carefully consider rainfall structure.