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High-entropy alloys (HEAs) and medium-entropy alloys (MEAs), have received much attention for developing nuclear materials because of their excellent irradiation tolerance. Herein, the formation and evolution of radiation-induced defects in Ni–Co–Fe MEA and pure Ni are investigated and compared using molecular dynamics simulation. It is observed that the defect recombination rate of ternary Ni–Co–Fe MEA is higher than that of pure Ni, which is mainly because, in the process of cascade collision, the energy dissipated through atom displacement decreases with increasing the chemical disorder. Consequently, the heat peak phase lasts longer, and the recombination time of the radiation defects (interstitial atoms and vacancies) is likewise longer, with fewer deleterious defects. Moreover, by studying the formation and evolution of dislocation loops in Ni–Co–Fe alloys and Ni, it is found that the stacking fault energy in Ni–Co–Fe decreases as the elemental composition increases, facilitating the formation of ideal stacking fault tetrahedron structures. Hence, these findings shed new light on studying the formation and evolution of radiation-induced defects in MEAs.