VQ motif-containing (VQ) proteins are cofactors of transcriptional regulation that are widely involved in plant growth and development and respond to various stresses. However, the functions of VQs participated in drought tolerance have been rarely characterized in wheat. In this study, we performed a comprehensive analysis of wheat VQ protein family. Cis-elements analysis found that the promoter region of TaVQ genes involved stress responses, hormone responses, growth and development, and WRKY binding elements. TaVQ2 was significantly up-regulated by drought stress and encoding a nuclear and cytoplasm localized protein. Overexpression of TaVQ2 in transgenic Arabidopsis plant caused enhanced drought tolerance by higher survival rates, germination rates and lateral root number compared to WT. After drought treatments, the activity of superoxide dismutase, catalase, and peroxidase as well as the contents of proline were higher, while the malondialdehyde contents were lower in transgenic Arabidopsis. Furthermore, TaVQ2 also enhanced the drought tolerance in transgenic wheat. Moreover, several genes related to the stress including TaRD22, TaCRT1, TaDREB, and TaDHN1 were significantly up-regulated in transgenic wheat than those of control. These results demonstrated that TaVQ2 confers drought tolerance in Arabidopsis and wheat. Taken together, our study provides evidence that the TaVQ2 plays role in tolerance of wheat against drought stress, which establishes a foundation for further research on the mechanism of action of TaVQ2 proteins with respect to drought stresses.