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Background Potato ( Solanum tuberosum  L.), the world’s third most important crop, is frequently thought to be sensitive to moderately sensitive to drought, and yield has fallen considerably over consecutive stress periods. Drought produces a wide range of responses in potato, from physiological alterations to variations in growth rates and yield. Knowledge about these responses is essential for getting a full understanding of drought-tolerance mechanism in potato plants which will help in the identification of drought-tolerant cultivars. Results A set of 21 commercial potato cultivars representing the genetic diversity in the Middle East countries market were screened for drought tolerance by measuring morpho-physiological traits and tuber production under in vitro and field trials. Cultivars were exposed to drought stress ranging from no drought to 0.1, 0.2 and 0.3 mol L −1  sorbitol in in vitro-based screening and 60, 40 and 20% soil moisture content in field-based screening. Drought stress adversely affected plant growth, yield and cultivars differed for their responses. Shoots and roots fresh weights, root length, surface area of root, no. of roots, no. of leaves, leaf area, plant water content %, K +  content, under in vitro drought treatments and shoots fresh and dry weights, no. of tubers and tuber yield under field drought treatments were examined and all decreased due to drought. The stress tolerance index decreased with increasing drought in examined cultivars; nevertheless, it revealed a degree of tolerance in some of them. Grouping cultivars by cluster analysis for response to drought resulted in: (i) a tolerant group of five cultivars, (ii) a moderately tolerant group of 11 cultivars, and (iii) a sensitive group of five cultivars. Furthermore, stress-related genes, i.e.,  DRO ,  ERECTA ,  ERF ,  DREB  and  StMYB  were up-regulated in the five cultivars of the tolerant group. Likewise, the stomatal conductance and transpiration explained high correlation with the tuber yield in this group of cultivars. Conclusion The diversity in germplasm indicated that potato cultivars can be developed for production under certain degrees of drought. Some cultivars are good candidates to be included in drought-tolerant breeding programs and recommended for cultivation in drought-stricken regions. Graphical Abstract

Response of potato (Solanum tuberosum L.) cultivars to drought stress under in vitro and field conditions