Chlorophenols are compounds with high toxicity, poor biodegradability, and carcinogenic and recalcitrant properties. This work studies, for the first time, the destruction and detoxification of 2-chlorophenol (2-CP) in water using 60Co gamma radiation under different conditions including varied radiation doses, addition of hydrogen peroxide (H2O2), and varied pH values. High-performance liquid chromatography (HPLC) and ion chromatography (IC) confirmed a successful degradation of 2-CP to primarily yield phenol molecules and chloride anions. A radiation dose as low as 25 kGy achieved approximately 90% removal of 50–150 ppm of 2-CP in neutral water. However, the addition of a strong oxidizer such as H2O2 to 2-CP solutions reduced the required dose to achieve 90% removal to at least 1.3-fold. The reduction in radiation doses was also observed in acidic and alkaline media, reducing the required doses of 90% removal to at least 0.4-fold. It was imperative to study the toxicity levels of the oxidation by-products to provide directions for the potential applicability of this technology in water treatment. Toxicology Microtox® bioassay indicated a significant reduction in the toxicity of the degradation by-products and the detoxification was further enhanced by the addition of H2O2 and changing the pH to more acidic or alkaline conditions. These findings will contribute to the knowledge of the removal and detoxification of such challenging environmental contaminant and could be potentially applied to other biologically resistant compounds.