Summary Drought stress profoundly hampers both plant growth and crop yield. To combat this, plants have evolved intricate transcriptional regulation mechanisms as a pivotal strategy. Through a genetic screening with rice genome‐scale mutagenesis pool under drought stress, we identified an APETALA2/Ethylene Responsive Factor, namely OsERF103, positively responds to drought tolerance in rice. Combining chromatin immunoprecipitation sequencing and RNA sequencing analyses, we pinpointed c. 1000 genes directly influenced by OsERF103. Further results revealed that OsERF103 interacts with Stress‐responsive NAC1 (SNAC1), a positive regulator of drought tolerance in rice, to synergistically regulate the expression of key drought‐related genes, such as OsbZIP23 . Moreover, we found that OsERF103 recruits a Su(var)3‐9,enhancer of zeste and trithorax‐domain group protein 705, which encodes a histone 3 lysine 4 (H3K4)‐specific methyltransferase to specifically affect the deposition of H3K4me3 at loci like OsbZIP23 and other genes linked to dehydration responses. Additionally, the natural alleles of OsERF103 are selected during the domestication of both indica and japonica rice varieties and exhibit significant geographic distribution. Collectively, our findings have unfurled a comprehensive mechanistic framework underlying the OsERF103‐mediated cascade regulation of drought response. This discovery not only enhances our understanding of drought signaling but also presents a promising avenue for the genetic improvement of drought‐tolerant rice cultivars.