Typically, pathogens deploy virulence effectors to disable defense. Plants defeat effectors with resistance proteins that guard effector targets. Here, we show that a pathogen exploits a resistance protein by activating it to confer susceptibility. Interactions of victorin, an effector produced by the necrotrophic fungusCochliobolus victoriae, TRX-h5, a defense-associated thioredoxin, and LOV1, an Arabidopsis susceptibility protein, recapitulate the guard mechanism of plant defense. In LOV1's absence, victorin inhibits TRX-h5 resulting in compromised defense but not disease by C. victoriae. In LOV1's presence, victorin binding to TRX-h5 activates LOV1 and elicits a resistance-like response that confers disease susceptibility. We propose that victorin is or mimics a conventional pathogen virulence effector that was defeated by LOV1 and confers virulence to C. victoriae solely because it incites defense.