The breakup process in quiescent atmosphere and high-speed cross-flow is numerically simulated. Three-dimensional RANS equations with the K -epsilon turbulence model are solved using commercial CFD software. Different droplet breakup models, namely, TAB, ETAB, Ritz-Diwakar, and KH-RT models are studied to assess their predictive capability in characterizing spray in high-speed cross-flow. The validation test cases include liquid injection into quiescent atmosphere, and subsonic and supersonic cross-flow. Computed droplet velocity, droplet size, and spray penetration are compared with the experimental/numerical data available in the literature. For diesel injection in quiescent atmosphere, computed spray penetration matches reasonably well with the experimental data. For subsonic cross-flow, although the penetration height is underpredicted, SMD distribution and particle velocity match reasonably well with the experimental data. The ETAB model captures the SMD values at different locations and velocities better with experimental data in comparison to the TAB model. For the supersonic cross-flow case, penetration height and SMD have a good match with the experimental data. The Stokes drag model performs better than the high-Mach and dynamic drag models. Droplet drag law for supersonic flow needs to be revised to have better predictive capability of spray characteristics in high-speed flow.