The rice RING-type E3 ligase BLAST AND BTH-INDUCED 1 (OsBBI1) confers broad-spectrum resistance against multiple races of blast fungus. In this study, we report the underlying mechanism of OsBBI1 in rice immunity. OsBBI1 ubiquitinates and mediates the degradation of multiple JA signaling co-repressors including OsJAZ6, OsJAZ7, OsJAZ8, and OsNINJA1, which negatively regulate rice resistance against blast and bacterial leaf blight diseases by affecting pathogen-induced reactive oxygen species (ROS) accumulation and pattern-triggered immune responses. OsBBI1 inhibits the negative immune functions of OsJAZ6 and OsNINJA1 in chitin-triggered ROS burst. OsBBI1 and OsJAZ6 interact with OsNINJA1, while OsJAZ6 interacts with Myelocytomatosis protein 2 (OsMYC2) and OsMYC3, which positively contribute to rice blast resistance. OsMYC2 regulates the transcription of a large set of genes through binding to the G-box elements (CACGTG) in their promoters, among which OsOXO4, a previously identified immune positive gene, and OsZIP9 were identified as direct targets of OsMYC2. Moreover, OsMYC2 forms homodimers and heterodimers with OsMYC3, which plays a synergistic role in OsMYC2-mediated activation of target gene transcription. These findings delineate a regulatory network in which OsBBI1 ubiquitinates multiple JA co-repressors for degradation to release OsMYC2, which directs the transcription of downstream target genes to activate rice immune responses.