Full-scale experimental and computational fluid dynamics (CFD) methods were used to investigate buoyancy-driven single-sided natural ventilation with large openings. Detailed airflow characteristics inside and outside of the room and the ventilation rate were measured. The experimental data were used to validate two CFD models: Reynolds averaged Navier-Stokes equation (RANS) modeling and large eddy simulation (LES). LES provides better results than the RANS modeling. With LES, the mechanism of single-sided ventilation was examined by turbulence statistical analysis. It is found that most energy is contained in low-frequency regions, and mean flow fields play an important role.