Water deficit or drought is one of the most severe factors limiting plant yield or fruit quality. Thus, water availability for irrigation is decisive for crop success, such as the case of highbush blueberry (Vaccinium corymbosum L.). Therefore, drought stress may compromise blueberry production due to lower fruit weight or fruit yield. Despite this, it is unclear if there is any difference in the response of blueberry cultivars to water deficit, either in terms of physiological and molecular parameters, or in terms of their sensitivity or resistance to drought. In this study, we determined the effect of drought on different physiological parameters in blueberry plants (relative water content (RWC), photochemical efficiency of photosystem II (Fv/Fm), Carbon Isotopic Discrimination, and proline content) in six V. corymbosum cultivars. We also explored molecular responses in terms of gene expression coding for late embryogenesis abundant proteins. Finally, we estimated cultivar water deficit resistance using an integrative model based on physiological results. Upon water deficit conditions, we found reductions in Fv/Fm, RWC, and isotopic discrimination of 13C (Δ13C), while proline content increased significantly for all cultivars. Additionally, we also found differences in the estimated water deficit resistance index. These results indicate differences in water deficit resistance, possibly due to variations in cultivars’ genetic composition.