Orange G (OG), a typical azo dye in textile wastewaters, has been the subject of intense investigations. This study investigated oxidative degradation of OG in aqueous solution by persulfate (PS) activated with pyrite. A complete destruction of OG was achieved within 60 min in the pyrite/PS system. Lower solution pH, smaller pyrite particles and higher pyrite dosage was beneficial for OG degradation. Higher PS concentration was also in favour of OG degradation, but excess PS would decrease the removal efficiency of OG. The addition of HCO3− and H2PO4− but Cl− had inhibitory effects on the destruction of OG. The results of quenching experiments and electron paramagnetic resonance tests proved that SO4•− and •OH were the dominant reactive species responsible for OG degradation in the pyrite/PS system. The azo bond, naphthalene ring and benzene ring of OG were all destroyed by the generated reactive species. The mineralization rate of OG reached 34.4% after 60 min of reaction. This work will provide information for understanding azo dye degradation by pyrite activated PS.