Water deficit is a key limiting factor for limiting yield in maize (Zea mays L.). It is crucial to elucidate the molecular regulatory networks of stress tolerance for genetic enhancement of drought tolerance. The mechanism of drought tolerance of maize was explored by comparing physiological and transcriptomic data under normal conditions and drought treatment at polyethylene glycol- (PEG-) induced drought stress (5%, 10%, 15%, and 20%) in the root during the seedling stage. The content of saccharide, SOD, CAT, and MDA showed an upward trend, proteins showed a downward trend, and the levels of POD first showed an upward trend and then decreased. Compared with the control group, a total of 597, 2748, 6588, and 5410 differentially expressed genes were found at 5%, 10%, 15%, and 20% PEG, respectively, and 354 common DEGs were identified in these comparisons. Some differentially expressed genes were remarkably enriched in the MAPK signaling pathway and plant hormone signal transduction. The 50 transcription factors (TFs) divided into 15 categories were screened from the 354 common DEGs during drought stress. Auxin response factor 10 (ARF10), auxin-responsive protein IAA9 (IAA9), auxin response factor 14 (ARF14), auxin-responsive protein IAA1 (IAA1), auxin-responsive protein IAA27 (IAA27), and 1 ethylene response sensor 2 (ERS2) were upregulated. The two TFs, including bHLH 35 and bHLH 96, involved in the MAPK signal pathway and plant hormones pathway, are significantly upregulated in 5%, 10%, 15%, and 20% PEG stress groups. The present study provides greater insight into the fundamental transcriptome reprogramming of grain crops under drought.