To date, the majority of numerical modelling [computational fluid dynamics (CFD)] studies on long-span bridges have been carried out on scaled physical models, and without field-data for validation. For the first time, a full-scale bridge aerodynamic CFD study was conducted in this paper. A full-scale three-dimensional CFD model of the middle span and central tower of the Queensferry Crossing, United Kingdom, was created. The aim of this work was accurately simulating the wind field around the bridge. The CFD simulations were developed in OpenFOAM with the k − ω SST turbulence model. Atmospheric boundary layer inflows were configured based on wind profiles provided by a full-scale Weather Research and Forecasting (WRF) model. CFD predictions were validated with field data which were collected from an on-site Structural Health Monitoring System. The simulated fluctuating wind field closely satisfied the characteristic of field data and demonstrated that the modelling approach had good potential to be used in practical bridge aerodynamic studies. Meanwhile, comparisons and sensitivity analyses on mesh density provided a reference modelling approach for any future works on full-scale bridge aerodynamic models. Additionally, a cylindrical-like domain was applied in bridge aerodynamics for the first time and verified as being a convenient and reliable way to be used in bridge studies that involve changes in yaw angle.