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In the hydrological sciences, the outstanding challenge of regional modeling requires to capture common and event-specific hydrologic behaviors driven by rainfall spatial variability and catchment physiography during floods. The overall objective of this study is to develop robust understanding and predictive capability of how rainfall spatial variability influences flood peak discharge relative to basin physiography. A machine-learning approach is used on a high-resolution dataset of rainfall and flooding events spanning 10 years, with rainfall events and basins of widely varying characteristics selected across the continental United States. It overcomes major limitations in prior studies that were based on limited observations or hydrological model simulations. This study explores first-order dependencies in the relationships between peak discharge, rainfall variability, and basin physiography, and it sheds light on these complex interactions using a multidimensional statistical modeling approach. Among different machine-learning techniques, XGBoost is used to determine the significant physiographical and rainfall characteristics that influence peak discharge through variable importance analysis. A parsimonious model with low bias and variance is created that can be deployed in the future for flash flood forecasting. The results confirm that, although the spatial organization of rainfall within a basin has a major influence on basin response, basin physiography is the primary driver of peak discharge. These findings have unprecedented spatial and temporal representativeness in terms of flood characterization across basins. An improved understanding of subbasin scale rainfall spatial variability will aid in robust flash flood characterization as well as with identifying basins that could most benefit from distributed hydrologic modeling. Significance Statement: To improve understanding of the effect of precipitation on floods, a machine-learning workflow is designed to scrutinize hydrological processes and is applied on a database of flood events over the United States. The model accurately reproduces observed maximum streamflow. It reflects physical hydrologic behavior that is consistent across basins, thereby addressing the challenge of regional modeling and improving upon traditional hydrological models. Rainfall spatial variability has a major influence on flood peak discharge, although basin geomorphology is the primary driver. This grants an improved understanding of the conditions under which floods are generated, allowing for better predictions and warning. [ABSTRACT FROM AUTHOR]