Inhibiting pathogen chemotaxis is a promising strategy for reducing disease pressure. However, this strategy is currently in the proof-of-concept stage. Here, Phytophthora sojae was used as a model, as its biflagellated zoospores could sense genistein, a soybean root exudate, to navigate host and initiate infection. We identify P. sojae IRK1 (isoflavone-insensitive receptor kinase 1) as a receptor for genistein, with PsIRK2 functioning as a coreceptor that enhances the binding affinity of PsIRK1 to genistein and regulates chemotaxis by phosphorylating G protein α subunit. Last, we identify an antagonist, esculetin, which disrupts the PsIRK1-genistein interaction, thereby preventing P. sojae infection by repelling zoospores. Our findings reveal the mechanism by which P. sojae senses host genistein and demonstrate a strategy for disease prevention by targeting the chemoreceptor.