In the agricultural field, blanching is a technique used to obtain tender, sweet, and delicious water dropwort stems by blocking sunlight. The physiological and nutritional parameters of blanched water dropwort have been previously investigated. However, the molecular mechanism of blanching remains unclear. In the present study, we investigated transcriptomic variations for different blanching periods in the stem of water dropwort (pre, mid, post-blanching, and control). The results showed that many genes in pathways, such as photosynthesis, carbon fixation, and phytohormone signal transduction as well as transcription factors (TFs) were significantly dysregulated. Blanched stems of water dropwort showed the higher number of downregulated genes in pathways, such as photosynthesis, antenna protein, carbon fixation in photosynthetic organisms, and porphyrin and chlorophyll metabolism, which ultimately affect the photosynthesis in water dropwort. The genes of hormone signal transduction pathways (ethylene, jasmonic acid, brassinosteroid, and indole-3-acetic acid) showed upregulation in the post-blanched water dropwort plants. Overall, a higher number of genes coding for TFs, such as ERF, BHLH, MYB, zinc-finger, bZIP, and WRKY were overexpressed in blanched samples in comparison with the control. These genes and pathways participate in inducing the length, developmental processes, pale color, and stress tolerance of the blanched stem. Overall, the genes responsive to blanching, which were identified in this study, provide an effective foundation for further studies on the molecular mechanisms of blanching and photosynthesis regulations in water dropwort and other species.