Magnaporthe oryzae is the causal agent of rice blast disease, leading to enormous losses of rice production. Here, we characterized a basic leucine zipper (bZIP) transcription factor, Moatf1, in M. oryzae, a homolog of Schizosaccharomyces pombe ATF/CREB that regulates the oxidative stress response. Moatf1 deletion caused retarded vegetative growth of mycelia, and the Moatf1 mutant exhibited higher sensitivity to hydrogen peroxide (H(2)O(2)) than did the wild-type strain. The mutant showed severely reduced activity of extracellular enzymes and transcription level of laccases and peroxidases and exhibited significantly reduced virulence on rice cultivar CO-39. On rice leaf sheath, most of the infectious hyphae of the mutant became swollen and displayed restricted growth in primary infected cells. Defense response was strongly activated in plants infected by the mutant. Diamino benzidine staining revealed an accumulation of H(2)O(2) around Moatf1 mutant appressoria and rice cells with Moatf1 hyphae that was absent in the wild type. Inhibition of the plant NADPH oxidase by diphenyleneiodonium prevented host-derived H(2)O(2) accumulation and restored infectious hyphal growth of the mutant in rice cells. Thus, we conclude that Moatf1 is necessary for full virulence of M. oryzae by regulating the transcription of laccases and peroxidases to impair reactive oxygen species-mediated plant defense.