In the present work, the sonocatalytic degradation of sodium isopropyl xanthate (SIPX) was investigated in the presence of Cu2S nanoparticles. Cu2S nanoparticles were produced by means of a high-energy planetary mechanical ball milling method within the processing times of 0.5, 1.5, 3 and 4.5 h. The physical and chemical characteristics of Cu2S particles were studied before and after ball milling process using various analytical techniques, including X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscope (SEM) coupled Energy-dispersive X-ray spectroscopy (EDX), atomic absorption spectroscopy (AAS) and nanoparticles size distribution (NSD). The XRD pattern of the samples confirmed the presence of tetragonal and cubic crystalline phases of Cu2S. In addition, the results of SEM and NSD analysis showed that the increase in the ball milling time from 0.5 to 4.5 h notably decreased the size of nanoparticles to the range of 20–40 nm. Furthermore, AAS result showed that the concentration of Cu+ ions was much lower than that of the accepted value in the aqueous media (0.009 mg/L) after 60 min of the sonocatalysis. The study on the effects of the main key parameters showed that 93.99% of SIPX (10 mg/L) was removed during 60 min of the sonocatalytic process under the optimum conditions: pH of 7.3, Cu2S concentration of 1.5 g/L, and ultrasonic power of 150 W. The sonocatalytic degradation mechanism was thoroughly examined in the presence of different organic and inorganic scavenger compounds, including ethanol, EDTA, NaCl and Na2SO4. The obtained results confirmed OH and holes (h+) as the dominant oxidizing species in Cu2S catalyzed sonolysis. In order to get the benefits of the integrated sonocatalytic process, different rate enhancing compounds were introduced into the system. For the first time, the S2O82− and Cu2S catalyzed sonolysis (US/Cu2S/S2O82−) system was introduced as an efficient and novel sonocatalytic system for fast degradation of SIPX. Moreover, the phyto-toxicological assessments proved the reduction in the toxicity of the sonocatalytic-treated SIPX solution by increase in the reaction time, from 20 to 60 min.