Molecular dynamics simulations were used to investigate the effect and mechanism of the angle (θ) between the plane of void center formation and the loading direction on void growth and coalescence behavior in single-crystal nickel under uniaxial tension. The results show that the yield stress and average flow stress of single-crystal nickel decrease with increasing θ, and the rate of stress decrease accelerates with increasing θ. When θ=90° (loading direction perpendicular to the plane of void center), the independent growth time of voids in single-crystal nickel is the shortest and void coalescence occurs first, leading to the most easily entering the softening stage. This is due to the fastest growth rate of void volume fraction and damage evolution rate in single-crystal nickel when θ=90°. When θ=90°, the significant reduction of 1/6<112> (Shockley) dislocation length and the maximum transformation rate of atomic number from FCC crystal structure to Other and HCP crystal structures in single-crystal nickel lead to the fastest damage evolution rate and the most severe damage level when θ=90°. It is worth noting that voids in single-crystal nickel are most likely to coalesce when θ=90°, due to the larger tensile stress on the void surface under this condition. Through this work, the aim is to reveal the void coalescence behavior and mechanism of metallic materials under high strain rates, and to provide theoretical guidance for understanding their softening behavior and fracture mechanism.