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Nitrous oxide (N2O) is a potent greenhouse gas that also contributes to ozone depletion. Recent studies have identified river corridors as significant sources of N2O emissions. Surface water-groundwater (hyporheic) interactions along river corridors induce flow and reactive nitrogen transport through riparian sediments, thereby generating N2O. Despite the prevalence of these processes, the controlling influence of physical and geochemical parameters on N2O emissions from coupled aerobic and anaerobic reactive transport processes in heterogeneous riparian sediments is not yet fully understood. This study presents an integrated framework that combines a flow and multi-component reactive transport model (RTM) with an uncertainty quantification and sensitivity analysis tool to determine which physical and geochemical parameters have the greatest impact on N2O emissions from riparian sediments. The framework involves the development of thousands of RTMs, followed by global sensitivity and responsive surface analyses. Results indicate that characterizing the denitrification reaction rate constant and permeability of intermediate-permeability sediments (e.g., sandy gravel) are crucial in describing coupled nitrification-denitrification reactions and the magnitude of N2O emissions. This study provides valuable insights into the factors that influence N2O emissions from riparian sediments and can help in developing strategies to control N2O emissions from river corridors