The δ13C value is regarded as an important indicator for tolerance to drought stress (DS), which is a severe abiotic stress that influences rice productivity. However, exploration of drought-responsive genes (DRGs) related to δ13C regulation is less reported. In this study, we investigated the natural variation in δ13C values in 102 japonica rice accessions. Among them, two rice accessions with contrasting δ13C values, Longdao 10 (LD10, DS-tolerant) and Binxu (BX, DS-sensitive), were used for further analysis. LD10 possesses better drought resistance with 2% lower δ13C values, 35% lower stomatal length and density, 33% lower water loss, and 11% lower stomatal conductance in comparison to BX. Transcriptome analysis shows that there are 2325 and 1378 differentially expressed genes (DEGs) induced by DS in LD10 and BX at the tillering stage, respectively, while there are 1076 and 492 DEGs in LD10 and BX at the graining stage, respectively. In total, 21 overlapped DEGs (defined as DRGs) were identified due to DS effects across two rice accessions over two stages. Among them, the expression levels of six genes, including chloride transporter (CLT1) and photosystem II polypeptide (PSBP), were further tested using qRT-PCR. Furthermore, we found that four methyltransferase genes were upregulated in BX compared to LD10 under DS. Consistently, the methylation levels of CLT1 and PSBP were higher along both promoter and CDS regions for CG, CHG, and CHH types. This study highlights the importance of the expression of these DRGs in response to DS and provides deep insights into DNA methylation-driven gene expression conferring different drought responses in rice.