An Eulerian–Lagrangian mathematical/computational methodology is employed for large-eddy simulation (LES) and detailed study of turbulent mixing in jet in cross-flow (JICF) configuration. Accurate prediction of mixing in JICF is crucially important to the development of advanced combustion systems. A high-order multiblock finite difference (FD) computational algorithm is used to solve the Eulerian velocity and pressure equations in a generalized coordinate system. The composition field, describing the mixing, is obtained from the filtered mass density function (FMDF) and its stochastic Lagrangian Monte-Carlo (MC) solver. Our simulations are shown to accurately predict the important flow features present in JICF such as the counter-rotating vortex pair (CVP), horseshoe, shear layer, and wake vortices. The consistency of the FD and MC parts of the hybrid LES/FMDF model is established for the simulated JICF in various conditions, indicating the numerical accuracy of the model. The effects of parameters influencing the jet penetration, entrainment, and turbulent mixing such as the jet velocity profile, and jet pulsation are investigated. The results show that the jet exit velocity profile significantly changes the trajectory and mixing of injected fluid. The jet pulsation is also shown to enhance the mixing depending on the flow Strouhal number. The LES/FMDF results are shown to be in good agreement with the available experimental data, confirming the reliability of LES/FMDF method for numerical simulation of turbulent mixing in complex flow configurations.