To investigate irradiation-induced embrittlement, molecular dynamics (MD) simulations were applied to explore helium (He) bubble evolution and deformation of single crystal α-Fe. The results show, at 800 K, formation kinetics of He bubbles are considered for two diffusion regimes due to He concentration: One is long-range diffusion of He atoms (< 0.1 at.%), and the other is short-range diffusion (> 0.1 at.%). In long-range diffusion, dislocations play a significant role on the size and spatial distributions of He clusters. He atoms are easier to segregate on dislocations, and therefore, average size of He clusters is increasing with increasing He concentration. In short-range diffusion, the influence of dislocations is rather weaker. He atoms tend to form He clusters by self-trapping, thus leading to decreasing average size. But, total number is monotonically increasing within the entire range (0–1 at.%). In tensile process, with increasing He concentration, yield stress is monotonically decreasing but plasticity is firstly increasing then decreasing. Especially, at 0.05 and 0.1 at.%, larger He bubbles with discrete distribution enhance deformability and promote dislocation multiply. In addition, for different He distributions, two growth mechanisms of He bubbles can be summarized: One is He bubble–He bubble coalescence, and the other is He bubble–void coalescence.