Calcite, the most stable polymorph of calcium carbonate (CaCO3), attracts growing attention due to its wide applications in many fields, such as composite materials, food industry, biomineralization, and dating of archeological and geological objects. Our study shows the influence of UV, X-ray and γ-radiation on the mechanical and physicochemical properties of calcite at the nanoscale. Using nanoindentation technique we observed a clear detriment in the mechanical response (hardness and elastic modulus) of the calcite (104) surface after irradiation, most visible in the case of UV. Changes in mechanical properties were correlated with the accumulation of radiation defects detected using EPR spectroscopy, and information on chemical bonding and composition obtained through XPS analyses. Additionally, the efficiency in generating defects for all three types of radiation was compared, which allowed us to propose a possible mechanism of UV-induced formation of radiation defects in calcite.