Flood variability due to changes in climate is a major economic and social concern. Climate drivers can affect the amount and distribution of flood-generating precipitation through seasonal shifts in storm tracks. An understanding of how the drivers may change in the future is critical for identifying the regions where the magnitude of floods may change. Here we show the regions in the conterminous U.S. where seasonal changes in global-scale climate oscillations have driven a large part of the variability of flood magnitude. The regions are cohesive across multiple watershed boundaries suggesting that variability in floods is driven by regional climate influences. Correlations with climate indices indicate that floods in the western and southern U.S. are most affected by global-scale climate. The regions provide a useful approach for characterizing flood variability and for attributing climatic drivers on flood variability and magnitude.