Drought stress severely affects wheat yield, and Whirly (WHY) transcription factors (TFs) are essential in modulating plant tolerance to abiotic stresses. In this study, we identified six WHY members in the wheat wholegenome database, categorized into Group I and Group II, with three homologous WHY genes in each group. From the four selected drought-responsive candidate genes with upregulated expression, we focused on TaWHY2-6A, which was significantly upregulated under drought stress. Under drought conditions, TaWHY2-6A transgenic Arabidopsis exhibited significantly higher chlorophyll content and better growth status compared to wild-type (WT) plants, indicating that TaWHY2-6A enhances drought resistance in transgenic Arabidopsis. In contrast, wheat lines with silenced-TaWHY2-6A exhibited a more severe wilting phenotype following drought treatment, accompanied by elevated levels of H2O2 and O2.-, and reduced antioxidant enzyme activity. These findings suggest that the wheat TaWHY2-6A gene positively regulates drought resistance under drought stress. This research provides a theoretical basis and valuable genetic resources for drought-resistance breeding in wheat.