This article represents the natural continuation of the work by Rossano and De Stefano (2021), dealing with the computational fluid dynamics analysis of a shock wave interaction with a liquid droplet. Differently from our previous work, where a two-dimensional approach was followed, fully three-dimensional computations are performed to predict the aerodynamic breakup of a spherical water body due to the impact of a traveling shock wave. The present engineering analysis focuses on capturing the early stages of the breakup process under the shear-induced entrainment regime. The unsteady Reynolds-averaged Navier–Stokes approach is used to simulate the mean turbulent flow field in a virtual shock tube device with circular cross section. The compressible-flow-governing equations are numerically solved by means of a finite volume method, where the volume of fluid technique is employed to track the air–water interface. The proposed computational modeling approach for industrial gas dynamics applications is verified by making a comparison with reference numerical data and experimental findings, achieving acceptably accurate predictions of deformation and drift of the water body without being computationally cumbersome.