Drought is one of the most critical abiotic stresses influencing maize yield. Improving maize cultivars with drought tolerance using marker-assisted selection requires a better understanding of its genetic basis. In this study, a doubled haploid (DH) population consisting of 217 lines was created by crossing the inbred lines Han 21 (drought-tolerant) and Ye 478 (drought-sensitive). The population was genotyped with a 6 K SNP assay and 756 SNP (single nucleotide polymorphism) markers were used to construct a linkage map with a length of 1344 cM. Grain yield (GY), ear setting percentage (ESP), and anthesis–silking interval (ASI) were recorded in seven environments under well-watered (WW) and water-stressed (WS) regimes. High phenotypic variation was observed for all traits under both water regimes. Using the LSMEAN (least-squares mean) values from all environments for each trait, 18 QTL were detected, with 9 associated with the WW and 9 with the WS regime. Four chromosome regions, Chr. 3: 219.8–223.7 Mb, Chr. 5: 191.5–194.7 Mb, Chr. 7: 132.2–135.6 Mb, and Chr. 10: 88.2–89.4 Mb, harbored at least 2 QTL in each region, and QTL co-located in a region inherited favorable alleles from the same parent. A set of 64 drought-tolerant BC3F6 lines showed preferential accumulation of the favorable alleles in these four regions, supporting an association between the four regions and maize drought tolerance. QTL-by-environment interaction analysis revealed 28 edQTL (environment-dependent QTL) associated with the WS regime and 22 associated with the WW regime for GY, ESP, and ASI. All WS QTL and 55.6% of WW QTL were located in the edQTL regions. The hotspot genomic regions identified in this work will support further fine mapping and marker-assisted breeding of drought-tolerant maize.