Diclofenac (DCF) degradation in aqueous solution under electron beam (EB) irradiation after nanobubbling treatment was studied and compared with treatments using nanobubbling or EB irradiation alone. It was found that the removal efficiency of DCF increased by increasing the adsorbed dose, and it depended on the initial concentration of DCF in solution, being higher for the lower concentrations. Furthermore, when using the nanobubbling treatment alone, about 16% of the DCF was removed from the aqueous solution due to the OH radicals generated during the process. On the other hand, using EB treatment at 0.5 kGy, the degradation of DCF increased from 36% to 51% when adding a nanobubbling pretreatment before the EB radiation. At higher doses (5 kGy), the degradation of DCF was 96% using EB radiation and 99% using nanobubbling before EB radiation, indicating that the nanobubbling effect was not synergistic. With an increase in the adsorbed doses, EB radiation seemed to play a more important role on the degradation of DCF, probably due to the reactive species generated. Moreover, the solutions treated with nanobubbling and EB radiation presented higher COD values and radiolytic by-products with aromatic rings with chlorine. This work can support the development of innovative strategies to treat municipal wastewaters using ionizing radiation technologies.