Controlled generation of reactive oxygen species (ROS) is essential in biological, chemical, and environmental fields, and piezoelectric catalysis is an emerging method to generate ROS, especially in sonodynamic therapy due to its high tissue penetrability, directed orientation, and ability to trigger in situ ROS generation. However, due to the low piezoelectric coefficient, and environmental safety and chemical stability concerns of current piezoelectric ROS catalysts, novel piezoelectric materials are urgently needed. Here, we demonstrate a method to induce polarization of inert poly(tetrafluoroethylene) (PTFE) particles (<d > ~ 1-5 μm) into piezoelectric electrets with a mild and convenient ultrasound process. Continued ultrasonic irradiation of the PTFE electrets generates ROS including hydroxyl radicals (•OH), superoxide (•O2-) and singlet oxygen (1O2) at rates significantly faster than previously reported piezoelectric catalysts. In summary, ultrasonic activation of inert PTFE particles is a simple method to induce permanent PTFE polarization and to piezocatalytically generate aqueous ROS that is desirable in a wide-range of applications from environmental pollution control to biomedical therapy.