Despite its relevance, few studies to date have analysed the role of harvest index (HI) in the responsiveness of wheat (Triticum spp.) to elevated CO2 concentration ([CO2]) under limited water availability. The goal of the present work was to characterise the role of HI in the physiological responsiveness of durum wheat (Triticum durum Desf.) exposed to elevated [CO2] and terminal (i.e. during grain filling) water stress. For this purpose, the performance of wheat plants with high versus low HI (cvv. Sula and Blanqueta, respectively) was assessed under elevated [CO2] (700¿¿mol¿mol¿1 vs 400¿¿mol¿mol¿1 CO2) and terminal water stress (imposed after ear emergence) in CO2 greenhouses. Leaf carbohydrate build-up combined with limitations in CO2 diffusion (in droughted plants) limited the responsiveness to elevated [CO2] in both cultivars. Elevated [CO2] only increased wheat yield in fully watered Sula plants, where its larger HI prevented an elevated accumulation of total nonstructural carbohydrates. It is likely that the putative shortened grain filling period in plants exposed to water stress also limited the responsiveness of plants to elevated [CO2]. In summary, our study showed that even under optimal water availability conditions, only plants with a high HI responded to elevated [CO2] with increased plant growth, and that terminal drought constrained the responsiveness of wheat plants to elevated [CO2].