The threat to crop security posed by diverse bacterial and fungal pathogens is seriously deteriorating in the face of climate change. The challenge put global nutritional safety at extreme risk, and this problem is expected to become increasingly serious in the future. Therefore, it is crucial to identify genes conferring broad-spectrum disease resistance (BSDR) to various pathogens and to unravel the underlying regulatory signaling pathways. WRKY transcriptional regulatory cascades play important roles in plant immunity. However, the signaling pathways are complex and far from fully characterized. Here, we demonstrated that OsWRKY65 enhances rice immunity against Fusarium fujikuroi and Xanthomonas oryzae pv. oryzae (Xoo) by controlling the expression of genes encoding important resistance and susceptibility factors. OsWRKY65 confers BSDR to F. fujikuroi and Xoo in rice by activating a transcriptional regulatory cascade consisting of several OsWRKYs, including OsWRKY9, OsWRKY13, OsWRKY30, and OsWRKY113. In this study, we proposed a novel OsWRKY transcriptional regulatory cascade and identified several OsWRKYs involved in immunity against F. fujikuroi and/or Xoo. Our findings lay the foundation for further detailed mechanistic studies and for plant breeding for BSDR to fungal and bacterial pathogens.