Residual pharmaceutical compounds (PCs) are among the emerging organic contaminants detected in our water cycle. Diclofenac (Dic) is one of the commonly detected pharmaceutical contaminant in aquatic systems. This study was designed to investigate the degradation and mineralization of Dic in aqueous solutions by ionizing radiation emitted from radioactive Co60 under several conditions. Ultra-performance liquid chromatography, ion chromatography and TOC measurements confirmed the radiolytic degradation of Dic. The absorbed doses needed to degrade 99% Dic at 25, 50, 100, 190, 280, and 480 μM were 0.560, 0.950, 1.950, 4.000, 5.400, and 7.400 kGy, respectively. This process follows pseudo-first-order kinetics. The γ-ray/NO system decreased the dose required to degrade 99% to 1.47 kGy. The presence of bromide anions inhibits degradation. Remarkably, adding HO, SO, or NO promotes mineralization. Conversely, the absence of dissolved oxygen hinders mineralization. This study provides a viable finding that ionizing radiation are useful tolls to remedy water containing pharmaceutical organic compounds.