Transcriptomic changes in plants during drought stress give insights into the mechanisms with which plants stabilise their metabolic processes in order to cope with the drought condition. In potato, understanding such drought-induced transcriptomic changes is critical because prolonged field drought interferes with tuber formation and bulking period of potato development, which eventually affects yield. We hypothesised that phenotypic drought responses of potato genotypes may be linked to differences in transcriptomic changes. Using an RNA sequencing approach, we investigated such transcriptomic changes in leaves of three cultivars (Biogold, Hansa and Lady Rosetta) under drought. We found more differentially expressed genes (DEGs) in the tolerant cultivars, Lady Rosetta and Biogold, than in the sensitive cultivar (Hansa). The differential gene expression trend reflected the phenotypic drought responses of the cultivars. For instance, we found in both Biogold and Lady Rosetta but not in Hansa, an upregulation of genes involved in carbohydrate metabolism (e.g., Alpha-glucosidase), flavonoid biosynthesis (e.g., Flavanone 3 beta-hydroxylase), lipid biosynthesis/transfer (e.g., nonspecific Lipid Transfer Proteins), heat shock proteins and secondary metabolites like phenolics and lignins. Furthermore, a prolonged drought stress resulted in reduced DEGs in Biogold and Hansa, but not in Lady Rosetta that also maintained its tuber yield under such prolonged stress suggesting a more robust drought tolerance. Our findings suggest that a synergistic expression of genes involved in several different aspects of drought response is required in order to obtain a robust tolerance.