This work highlights the effect of proton irradiation in the presence of preexisting defects in the Nb-1Zr-0.1C alloy. To introduce the initial defects, the Nb-1Zr-0.1C alloy was subjected to cold rolling (10% and 20%) prior to irradiation. Characterization of the irradiated material was performed using detailed X-ray diffraction line profile analyses. The results, in terms of various microstructural parameters, revealed that the preexisting defects in these materials act as effective sinks for irradiation-induced defects during the initial irradiation. Electron backscattered diffraction analyses suggested that the fraction of low-angle grain boundaries plays a crucial role during irradiation and determines the outcome of the competing process between defect annihilation and defect production. Transmission electron microscopy analyses revealed that the black dots were coexisting with carbide precipitate in the cold-rolled Nb alloy after irradiation. Mechanical properties were also assessed by measuring microhardness to correlate with the changes in microstructure after irradiation. The change in yield strength calculated from the change in the microhardness value as a function of dose indicated that the 20% cold-rolled Nb alloy was more radiation resistant than the 10% cold-rolled Nb alloy at ambient temperature and a low-dose regime. To see the effect of alloying elements, similar studies were also carried out on pure Nb, and the results were compared with that of the Nb-1Zr-0.1C alloy. All these findings help to develop a better understanding of the behavior of the proton-irradiated Nb-1Zr-0.1C alloy in the presence of preexisting defects introduced by means of cold rolling prior to irradiation.