Abstract: Background and Objective: The sonochemical degradation of seven estrogen hormones (17α-estradiol, 17β-estradiol, estrone, 17α-dihydroequilin, 17α-ethinyl estradiol, estriol and equilin) in water and wastewater was investigated. Methodology: The effects of pH, presence of oxidants such as peroxide and persulfate were examined. Statistical 3D modeling was used as a tool to identify the correlation between the reaction rate constants, sample pH and estrogen molecular weight. Statistical analysis was performed using STATISTICA 10. Results: The results obtained in this study indicated that the rate of ultrasonic degradation in water and wastewater is influenced by the sample pH, oxidants and the dissolved organic content. More than 90% removal of all the estrogen hormones was achieved under basic pH conditions. The degradation process followed a pseudo-first order kinetic model with reaction rate constants ranging from 0.01-0.9 min–1. The degradation rate constants were observed to follow the order of deionized water>final effluent>secondary effluent>primary effluent. Conclusion: Optimization of the process conditions led to a 50-90% enhancement in the degradation kinetics, thereby making the process attractive for field applications.