Identifying drought stress regulatory genes is essential for the genetic improvement of maize yield. Deoxyribonucleic acid binding with one finger (Dof), a plant-specific transcription factor family, is involved in signal transduction, morphogenesis, and environmental stress responses. In the present study, by weighted correlation network analysis (WGCNA) and gene coexpression network analysis, 15 putative Dof genes that respond to drought and rewatering were identified from maize. A real-time fluorescence quantitative PCR showed that these 15 genes were strongly induced by drought and ABA treatment, and among them, ZmDof22 was highly induced by drought and ABA treatment. Its expression level increased nearly 200 times after drought stress and more than 50 times after ABA treatment. After the normal conditions were restored, the expression levels were almost 100 times and 40 times those before treatment, respectively. The Gal4-LexA/UAS system and transcriptional activation analysis indicate that ZmDof22 is a transcriptional activator regulating maize drought tolerance and recovery ability. Further, overexpressed transgenic and mutant plants of ZmDof22 by CRISPR/Cas9 show that the ZmDof22 improves maize drought tolerance by promoting stomatal closure, reduces water loss, and enhances antioxidant enzyme activity by participating in the ABA pathways. Taken together, our findings laid a foundation for further functional studies of the ZmDof gene family and provided insights into the role of the ZmDof22 regulatory network in controlling drought tolerance and recovery ability of maize.