In the Mediterranean area, climate change is associated with atmospheric CO2 concentration increases, enhanced temperatures and scarce water availability, limiting seriously crop yield and decreasing quality. The aim of this study was to investigate the effects of elevated CO2, elevated temperature and water deficit, acting individually and/or interacting, on vegetative and reproductive growth, substrate and plant water status, and must quality in fruit-bearing cuttings of two grapevine (Vitis vinifera L.) cultivars (red and white Tempranillo). In four temperature gradient greenhouses, eight treatments were applied, from fruit set to maturity: CO2 level (400 versus 700 ¿mol mol¿1), temperature (ambient versus ambient +4 °C), and water availability (full irrigation versus cyclic drought). Effects of climate change on grape yield and quality were cultivar dependent. Generally, red Tempranillo had more vegetative growth and grape yield than the white cultivar. Also, grape yield was less affected by the treatments than vegetative growth. Drought, especially under elevated temperature, drastically reduced vegetative growth, bunch fresh and dry weights in both cultivars. Interestingly, elevated CO2 attenuated these negative effects of drought. The effects of climatic factors on yield were not associated with a worse water status of the vegetative or reproductive organs. In red Tempranillo, the combination of elevated CO2, elevated temperature and drought reduced total polyphenol index (TPI), malic acid and increased color density, but did not modify anthocyanin concentration. In white Tempranillo, the combined action of the three factors associated with climate change modified only tartaric acid. In this latter cultivar, drought increased TPI under ambient temperature, regardless of CO2 level, when compared with full-irrigated plants. In conclusion, climate change-related factors (elevated CO2, elevated temperature and water deficit) individually (especially drought) and/or interacting affected to different extent red and white Tempranillo vegetative growth and yield. Drought combined with elevated temperatures reduced grapevine performance, and elevated CO2 mitigated such deleterious effect.