The thermomechanical behavior of materials is known to be sensitive to preexisting defects in their microstructure. In this paper, non-equilibrium molecular dynamics simulations have been used to investigate the effects of the microvoid size on the plastic deformation in single-crystal iron shock-compressed along the [001] crystallographic direction. The higher the microvoid radius, the faster the kinetics of dislocations. Thus, as the microvoid radius increases, the plastic activity evolves from a regime where the deformation is dominated by twin activities to a regime where both twin and dislocation activities play an essential role and then to a regime where the deformation is dominated by dislocation slip. Furthermore, in both defect-free and defective initial crystal states, the elastic precursor wave is observed to decay with propagation distance, resulting in a constitutive functional dependence of the yielding pressure, σE, on the plastic deformation rate, ε˙p. In the regime where both deformation twinning and dislocation slip play important roles, the constitutive behavior is consistent with the original Swegle–Grady model and is in overall agreement with experimental data and thermomechanical simulations.