Drought stress is one of the environmental cues that reduce crop yield. Under drought stress, abscisic acid (ABA) content in plants is increasing by inhibiting the expression of CYP genes involved in the ABA metabolism. However, little information is available regarding how epigenetic modification particpates the CYP gene-mediated drought stress response. In this study, we showed enhanced drought resistance in plants by increasing the H3K27me3 level of the CYP genes. Compared with wild-type Col-0, ref6 mutants or/and elf6ref6jmj13 mutants displayed enhanced drought resistance and higher ABA content, which is consistent with decreased CYP genes expression. ChIP-seq results showed that the level of H3K27me3 on the CYP genes in ref6 was significantly higher than that of the wild type. Moreover, EMSA assay showed that REF6 can bind to the CTCTGYTY motif in the intron region of CYP707A1 and CYP707A3. We also obtained a transgenic line by using the catalytically dead Cas9 (dCas9) protein to target the intron region of CYP707A1/A3. Compared with the control, transgenic line displayed more drought resistance and lower H3K27me3 level of CYP707A1/A3. Therefore, our results show that the drought resistance of plants can be improved by manipulating the H3K27me3 level of the CYP genes.