- Deficit irrigation techniques are widely used in commercial vineyards. Nevertheless, varieties respond differently to water availability, prompting the need to elucidate the physiological and molecular mechanisms involved in the interactions between genotypes and their environment. In the present study, the variability in berry metabolism under deficit irrigation was investigated in the field on Shiraz and Cabernet Sauvignon (CS), known for their hydraulic variability. Berry skin metabolite profiling of the two cultivars was performed by parallel GC–MS and LC-MS at four development stages. Under similar irrigation, the cultivars differed in stomata regulation. In response to water deficit, CS exhibited lessened loss in berry weight and milder metabolic alteration of berry-skin primary metabolites, as compared with Shiraz. The metabolic stress responses were shown to depend on berry phenology. Characteristic metabolic changes included a decrease in amino acids and TCA cycle intermediates from veraison onward. In contrast, water deficit induced the accumulation of stress-related metabolites such as: proline, beta-alanine, raffinose, nicotinate and ascorbate, to a greater extent in Shiraz. Polyphenol metabolism in response to water stress also underwent significant changes, unique to each cultivar. Results suggest a link between the vine hydraulics and water-deficit driven changes in the berry skin metabolism, with significant consequences on the metabolic composition of the fruit.