Nitrous oxide (N2O) emitted from biological nutrient removal activated sludge systems contributes significantly to the total carbon footprint of modern wastewater treatment plants. In the present study, N2O production and emissions were experimentally determined in a large-scale plant (220,000 PE) employing combined nitrogen (N) and phosphorus (P) removal. As a modelling tool, the Activated Sludge Model 2d (ASM2d) was extended with modules describing multiple N2O production pathways and N2O liquid-gas transfers. The new model was calibrated and validated using the results of laboratory experiments and full-scale measurements. Different operational strategies were evaluated following the proposed model-based procedure. Heterotrophic denitrification was found to be the predominant pathway of N2O production under both anoxic and aerobic conditions. This behaviour could primarily be attributed to the predominant abundance of heterotrophic denitrifiers over nitrifiers. Simulations revealed that the optimal solution for minimizing liquid N2O production is to set the dissolved oxygen concentration in the aerobic zone from 1 to 2 mg O2/L and to enhance the mixed liquor recirculation rate (MLR) (>500% of the influent flowrate) while not compromising effluent standards. Regarding the actual conditions, the potential reduction in the carbon footprint was estimated to be 10% by applying the proposed operational strategy. The results suggest that considerable improvements can be achieved without substantial upgrades and increased costs.