In plant–pathogen interaction, plants trigger reactive oxygen species (ROS) bursts to defend against pathogen invasion, while pathogens evolved antioxidant systems to scavenge ROS for infection. Our study reveals a novel regulatory mechanism of ROS adaptation and scavenging in the rice blast fungus Magnaporthe oryzae. We found that KatG1, a bifunctional catalase-peroxidase, acts as a ROS-responsive regulatory enzyme. During infection, the deacetylase Hos2 mediates the decrotonylation of KatG1 at K422, initiating the ROS clearance process. Decrotonylated KatG1 depolymerizes into monomers, interacts with the Hsp70 protein Ssb1, and translocates to the nucleus. Nuclear KatG1 promotes the dissociation of the Atf1-Tup1 complex, activating the expression of Atf1-mediated oxidoreductase genes and enhancing fungal infection. Moreover, we identified a small molecule, orcinol gentiobioside (OGB), that targets KatG1, inhibiting M. oryzae invasion. This study elucidates a new regulatory mechanism of ROS metabolism and stress adaptation in plant fungal infections and provides a potential target for fungicide development to control rice blast disease