Fe-Ni-Cr-based alloys, including alloy 800H, are used as structural materials in nuclear reactors such as the PWRs and BWRs, but also are considered as candidate materials for advanced reactors. In this work, we report a molecular dynamics (MD) study of the effect of irradiation and alloy composition on the microstructure and mechanical behavior of alloy 800H. Our results of primary irradiation damage suggest a larger spontaneous recombination distance for Cr compared to other alloy components, thereby suggesting that Cr may increase the tolerance of the alloy 800H to primary defect production. The progressive accumulation of irradiation events through cascade overlap results in the growth of defects and their agglomeration into clusters, but also induces the formation of dislocations. Irradiation-induced mechanical degradation was also investigated for the single crystal, and based on our observations two degradation mechanisms were proposed: the nucleation and glide of dislocations, promoted by the dynamics of interstitial atoms and vacancies defects under applied strain field, and the rapid activation of slip systems by the combined effect of the foregoing and generated dislocations, vacancies and interstitial atoms. We also found that increasing Ni or Cr substantially limits the irradiation-induced mechanical degradation. Finally, our MD findings highlight the strengthening of alloy 800H by increasing Ni content, and the degradation of the Young modulus induced by the increase of Cr content.