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This paper presents the results of a study on the influence of Y2O3 doping on the resistance to radiation damage and an assessment of structural changes associated with the accumulation of radiation defects in CeO2 microparticles under irradiation with heavy Xe22+ ions. The relevance of this study consists of the prospects for the use of CeO2 microparticles as materials and candidates of inert matrices of nuclear fuel. A method of solid-phase synthesis was applied to obtain microparticles with different concentrations of dopant. It included grinding of CeO2 and Y2O3 microparticles followed by thermal sintering at 1100 °C in an oxygen-containing medium to produce highly ordered microparticles. During the study of the structural characteristics of the synthesized microparticles, it was found that increasing the dopant concentration from 0.05 mol.% to 0.15 mol.% leads to an increase in the crystallinity degree as well as a decrease in dislocation density. According to the results of the assessment of the resistance of microparticles to radiation damage, it was found that an increase in the dopant concentration leads to a decrease in swelling and structural distortion by more than 2.5–3 times, which indicates an increase in the radiation resistance.