Within the current climate context, freshwater resources have become scarce. Agriculture, especially in rain-fed conditions, should deal with the need of increasing yields to contribute to food security under limiting water availability. Exploring underutilized crops such as Chenopodium quinoa (quinoa) has become a unique oppor-tunity as some of these crops possess the ability to tolerate several abiotic stresses, including drought. In line with this, this work aimed at evaluating the genotype-dependent response to drought by comparing the performance of different European-adapted cultivars (F14, F15, F16, and Titicaca). The results show that the cultivars here evaluated presented different mechanisms to cope with long-term water stress, including changes in phenology, morphology, or physiology. Among them, the cultivar F16 might be the most promising genotype to grow under water-limiting conditions as it presented a reduced foliar total surface (fewer branches and leaves) with higher chlorophyll contents and was able to increase Water Use Efficiency (WUE), reducing the stomatal conductance and keeping CO2 assimilation rates similar to well-watered conditions. These characteristics lead to F16 main-taining seed yield and increasing harvest index (HI) under water deficit conditions, making it a cultivar tolerant to drought. Furthermore, based on these results, we propose a model in which differences between a water-use efficient and a drought-sensitive genotype are presented. Altogether, we believe that this work will significantly contribute to broadening our understanding of how quinoa responds to long-term water stress highlighting genotype-related differences that will allow the selection of the best-adapted genotypes for water-limiting environments.