Our previous studies indicated that endophyte M7SB41 (Seimatosporiumsp.) can significantly enhance host plants powdery mildew (PM) resistance. To recover the mechanisms, differentially expressed genes (DEGs) were compared between E+ (endophte-inoculated) and E− (endophyte-free) plants by transcriptomics. A total of 4094, 1200 and 2319 DEGs between E+ and E− were identified at 0, 24, and 72 h after plants had been infected with PM pathogenGolovinomyces cichoracearum, respectively. Gene expression pattern analysis displayed a considerable difference and temporality in response to PM stress between the two groups. Transcriptional profiling analysis revealed that M7SB41 induced plant resistance to PM through Ca2+signaling, salicylic acid (SA) signaling, and the phenylpropanoid biosynthesis pathway. In particular, we investigated the role and the timing of the SA and jasmonic acid (JA)-regulated defensive pathways. Both transcriptomes and pot experiments showed that SA-signaling may play a prominent role in PM resistance conferred by M7SB41. Additionally, the colonization of M7SB41 could effectively increase the activities and the expression of defense-related enzymes under PM pathogen stress. Meanwhile, our study revealed reliable candidate genes from TGA (TGACG motif-binding factor), WRKY, and pathogenesis-related genes related to M7SB41-mediate resistance. These findings offer a novel insight into the mechanisms of endophytes in activating plant defense responses.