This study presents a non-equilibrium molecular dynamics simulation of the shock compression of a [1¯10]-oriented CoCrFeMnNi high-entropy alloy (HEA) at 77 K. The effects of different impact velocities on the mechanical properties were investigated in detail, as well as the changes in atomic microstructure and the formation of defects and dislocations under impact loading. In addition, the role of voids in the CoCrFeMnNi HEA was investigated. The results showed that with an increase in impact velocity, the average values of the atomic velocity, temperature, and stress increase. The phenomenon of double-wave separation of the elastic and plastic waves was apparent, and when the loading velocity increased, the propagation velocities of the elastic and plastic waves also increased incrementally. The change in the atomic microstructure and generation of dislocation defects further revealed the effect of different impact velocities on the CoCrFeMnNi HEA. The degree of change in the phase structure was positively correlated with the magnitude of the impact velocity; however, the number of dislocations and defects first increased to a maximum and then decreased with the increase in impact velocity. In addition, the void structure had almost no effect on the phase change of the HEA when subjected to impact loading, whereas the effect on dislocation defects was more pronounced.