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Drought stress exerts a significant impact on the growth, development, and yield of fruit trees. Cerasus humilis is an endemic drought‐resistant fruit tree in northern China. To elucidate the underlying mechanism of drought resistance in C. humilis, comprehensive physiological measurements and transcriptome analysis were conducted on the leaves of C. humilis subjected to 15‐ or 22‐days of drought stress. We identified multiple GO terms and KEGG pathways associated with the drought stress response by performing GO and KEGG analysis on DEGs. Furthermore, through the prediction of transcription factors (TFs) and analysis of their expression levels, we observed differential expression patterns among most members of stress‐responsive TF families as the duration of drought stress increased. WGCNA analysis was performed on the transcriptome to identify gene cluster modules that exhibited a strong correlation with the durations of drought. Subsequently, these modules underwent GO and KEGG enrichment analyses. The study revealed that the TF‐mediated lignin biosynthesis pathway, along with the plant hormone signal transduction pathway, played a prominent role in responding to drought stress of C. humilis. Gene profiling analysis, qRT‐PCR, and determination of phytohormone and lignin contents further supported this hypothesis. The hierarchical gene regulatory network was finally constructed based on DEGs from the aforementioned key enriched pathways to predict the gene regulatory mechanisms in response to stress for C. humilis. The findings from this study provide valuable insights into how C. humilis copes with drought stress while analyzing crucial gene pathways associated with its resistance from a TF perspective. This research is significant for the genetic breeding of economic forests.