This paper presents a new computational fluid dynamics (CFD) approach for the assessment of NOx emission. The methodology is validated against the experimental data of a heavy-duty gas turbine annular combustor. Since the NOx formation involves time scales that are different from the fuel oxidation time, this work defines the transport equation source terms for NOx basis on a dedicated NOx-Damköhler number. The latter parameter allows to properly distinguish the “in-flame” contribution from the “postflame” one. While the former is a mix of several mechanisms (prompt, N2O-pathway, thermal), the latter is dominated by the thermal contribution. The validation phase is developed in a large-eddy simulation (LES) framework where the extended turbulent flame speed model is implemented to consider the influence of both heat loss and strain rate on the progress variable source term. The accuracy of the model against the most important operability parameters of the combustor is verified. A strong focus on the fuel composition effect onto NOx is presented as well. For any simulated operating condition, the present methodology is able to provide a limited percentage error if compared with the data, considering also different combustion regimes. Leveraging this alignment, the last portion of the paper is dedicated to detailed postprocessing highlighting the role of some key factors on NOx formation. In particular, the focus will be dedicated to the impact of the fuel gas composition and the pilot split.