Indirect nitrous oxide (N2O) emissions from rivers are currently derived using poorly constrained default IPCC emission factors (EF5r) which yield unreliable flux estimates. Here, we demonstrate how hydrogeological conditions can be used to develop more refined regional-scale EF5r estimates required for compiling accurate national greenhouse gas inventories. Focusing on three UK river catchments with contrasting bedrock and superficial geologies, N2O and nitrate (NO3-) concentrations were analyzed in 651 river water samples collected from 2011 to 2013. Unconfined Cretaceous Chalk bedrock regions yielded the highest median N2O-N concentration (3.0 μg L-1), EF5r (0.00036) and N2O-N flux (10.8 kg ha-1 a-1). Conversely, regions of bedrock confined by glacial deposits yielded significantly lower median N2O-N concentration (0.8 μg L-1), EF5r (0.00016) and N2O-N flux (2.6 kg ha-1 a-1), regardless of bedrock type. Bedrock permeability is an important control in regions where groundwater is unconfined, with a high N2O yield from high permeability Chalk contrasting with significantly lower median N2O-N concentration (0.7 μg L-1), EF5r (0.00020) and N2O-N flux (2.0 kg ha-1 a-1) on lower permeability unconfined Jurassic mudstone. The evidence presented here demonstrates EF5r can be differentiated by hydrogeological conditions and thus provide a valuable proxy for generating improved regional-scale N2O emission estimates.