Background: Frequently occurring drought stress negatively affects the production of maize worldwide. Numerous efforts have been made to develop drought-tolerant maize lines and to explore drought tolerant mechanisms in maize. However, there is a lack of comparative studies on transcriptomic changes between drought-tolerant and control maize lines. Results: In the present study, we have developed a drought-tolerant maize mutant (C7-2t) by irradiating the seeds of maize inbred line ChangC7-2 (C7-2) with 60 Co-γ. Compared to its wild type C7-2, C7-2t exhibited a significantly delayed wilting and higher drought tolerance under both the controlled and field conditions, indicating its high water-holding ability. Transcriptomic profiling was performed to identify differentially expressed genes (DEGs) between C7-2 and C7-2t during drought. As a result, a total of 4552 DEGs were implied in drought tolerance of C7-2 and C7-2t. In particular, the expression of photosynthesis-related genes in C7-2 was inhibited, whereas these genes in C7-2t were almost unaffected under drought. Moreover, a specific set of the DEGs were involved in phenylpropanoid biosynthesis and taurine (hypotaurine) metabolism in C7-2t; these DEGs were enriched in cell components associated with membrane systems and cell wall biosynthesis. Conclusions: The drought tolerance of C7-2t was largely due to its high water-holding ability, stable photosynthesis (for supporting osmoregulation) and strengthened biosynthesis of cell walls under drought conditions.