Ultrasonic treatment for enhancing biological processes has recently attracted considerable attention in wastewater treatment. In this study, we systematically investigated the mixed liquor properties of activated sludge under ultrasonic treatment. The sludge samples were collected from the aerobic tank of a full-scale membrane bioreactor (MBR) treating municipal wastewater, and the volatile suspended solids (VSS) concentration was approximately 6.0 g/L. The results showed that ultrasonic treatment induced floc disintegration, organics release, temperature increase, microbial activity and pH variation. The maximum mg soluble chemical oxygen demand (COD) per mg VSS released was estimated to be 0.147 using the Monod equation. The exponential increase in the concentration of dissolved organic matter is related to the loss of relative heterotrophic bacterial activity. A sonolysis-cryptic growth model was demonstrated to be capable of describing ultrasonic sludge reduction, which would support the further development of ultrasonic treatment technology in activated sludge systems.