Large-eddy simulation (LES) is a useful approach for the simulation of turbulent flow and combustion processes in internal combustion engines. This study employs the ANSYS Forte CFD package and explores several key and fundamental components of LES, namely, the subgrid-scale (SGS) turbulence models, the numerical schemes used to discretize the transport equations, and the computational mesh. The SGS turbulence models considered include the classic Smagorinsky model and a dynamic structure model. Two numerical schemes for momentum convection, quasi-second-order upwind (QSOU) and central difference (CD), were evaluated. The effects of different computational mesh sizes controlled by both fixed mesh refinement and a solution-adaptive mesh-refinement approach were studied and compared.The LES models are evaluated and validated against several flow configurations that are critical to engine flows, in particular, to fuel injection processes. These configurations include a turbulent planar gas jet, an evaporating and non-reacting spray, and a reacting spray. In the gas-jet case, predicted time-averaged and root-mean-squared (RMS) flow speed and Reynolds stress are validated against experimental and Direct Numerical Simulation (DNS) data. Qualitative results, including the iso-surface of the Q-criterion are also presented. In the non-reacting spray case, predicted liquid and vapor penetrations are validated against data from the “Spray H” experiment of Engine Combustion Network (ECN). In the reacting spray case, predicted ignition-delay time and flame lift-off length using a detailed reaction mechanism are validated against the “Spray H” data from ECN. Based on these simulation results, recommended practices for the use of the SGS models, with respect to numerical schemes and mesh resolution, are summarized.