Drought stress impairs plant growth and poses a serious threat to maize (Zea mays) production and yield. Nevertheless, the elucidation of the molecular basis of drought resistance in maize is still uncertain. In this study, we identified ZmSCE1a, a SUMO E2-conjugating enzyme, as a positive regulator of drought tolerance in maize. Molecular and biochemical assays indicated that E3 SUMO ligase ZmMMS21 acts together with ZmSCE1a to SUMOylate histone acetyltransferase complexes (ZmGCN5-ZmADA2b). SUMOylation of ZmGCN5 enhances its stability through the 26S proteasome pathway. Furthermore, ZmGCN5-overexpressing plants showed drought tolerance performance. It alleviated accumulation, malondialdehyde content, and ion permeability. What's more, the transcripts of stress-responsive genes and abscisic acid (ABA)-dependent genes were also significantly upregulated in ZmGCN5-overexpressing plants under drought stress. Overexpression of ZmGCN5 enhanced drought-induced ABA production in seedlings. Taken together, our results indicate that ZmSCE1a enhances the stability of ZmGCN5, thereby alleviating drought-induced oxidative damage and enhancing drought stress response in maize.