The System of Rice Intensification (SRI) is an agricultural approach designed to boost rice yield, water efficiency, and pest control. When local rice varieties were grown using SRI and conventional methods, SRI resulted in improved root development, higher chlorophyll content, and increased uptake of secondary macronutrients. Alternate wetting and drying (AWD), a technique employed in SRI, can save up to 30% more water than traditional flooding. Nevertheless, the effect of water stress on gene expression in AWD is uncertain. In this study, the drought-sensitive lowland rice cultivar IR64 was used to analyze alterations in transcriptome profiles under alternate wetting and drying (AWD) and continuous flooding (CF) conditions. Field studies were conducted and irrigation regimes were implemented 40 days after sowing. AWD involves applying water only when the soil water potential reaches -40kPa and continues until harvest. Leaf samples collected during the early flowering stage (day 88) were sequenced using RNA-seq on an Illumina platform. To track alterations in the transcriptional response under different water conditions, reads were processed for differential expression (DE) using the QIAGEN CLC Genomics Workbench. In these samples, 204 genes were identified as having altered expression under water stress, with log2FC>1 and FDR<0.05, of which 40% were downregulated and 60% were upregulated. Os02g0756800, PLA2-II, and OsDREB1G exhibited the greatest variation in gene expression when subjected to water-stress conditions. These genes, known as phosphate-induced protein 1, are related to the apoplast, Phospholipase A2 family protein, and CRT/DRE binding factor 1, respectively. The apoplast is involved in a wide variety of activities, including intercellular signaling, plant–microbe interactions, and the transportation of water and nutrients. PLA2 is responsible for plant growth, development, stress responses, and defense signalling. OsDREB1G is responsible for activating transcription factors in response to drought and salt stress caused by high salinity and dehydration. This implies that the gene expression in rice cultivated in CF and AWD is significantly distinct owing to the adaptation of rice to the water stress response.