One of the main challenges to malaria elimination is the resilience of vectors, such as Anopheles arabiensis, that evade lethal exposure to insecticidal control measures or express resistance to their active ingredients. This study investigated a novel technology for population control that sterilizes mosquitoes using pyriproxyfen, a juvenile hormone analogue. Females of An. arabiensis were released in a semifield system divided into four equal sections, and each section had a mud hut sheltering a tethered cow providing a blood source for mosquitoes. In all sections, the inner mud hut walls and roofs were lined with black cotton cloth. In one-half of the sections, the cloth was dusted with pyriproxyfen. An overwhelming 96% reduction in adult production was achieved in pyriproxyfen-treated sections compared with control sections. This unprecedented level of control can be exploited to design new vector control strategies that particularly target existing behaviorally resilient and insecticide-resistant populations.