Quorum quenching (QQ) is a new and promising strategy that disrupts the quorum sensing system, a universal and important microbial communication that results in membrane biofouling and other various communal behaviors. A bacterial strain Z4 with a relatively high QQ ability was isolated from a wastewater treatment plant and identified as a Serratia sp. This is the first report of a bacterium belonging to the genus Serratia with such QQ ability. This strain not only degraded at least 93% of 10 μg/ml C8-HSL signaling molecules within 24 h, but also reduced the main bacterial by-products in sludge mixture, soluble microbial products (SMP) mass by 75%, and extracellular polymeric substances (EPS) by 37%, during wastewater treatment. Interestingly, the presence of strain Z4 in the sludge had an obvious impact on the microbial diversity of the sludge mixture during wastewater treatment. The results show that the isolated strain Z4 is a very potent strain for use in a QQ strategy, and the application and mechanism in biofouling mitigation should be further explored.