European rivers are under ecological threat by a variety of stressors. Nutrient pollution, soil erosion, and alteration in hydrology are considered the most common problems that riverine ecosystems are facing today. Not surprisingly, river monitoring activities in Europe have been intensified during the last few years to fulfil the Water Framework Directive (WFD) requirements. With this article, we present a nationwide assessment of the water quality and hydromorphological variability in Greek Rivers based on the results of the national monitoring program under the WFD. Water quality and hydromorphological data from 352 sites belonging to 221 rivers were explored with principal component analysis (PCA) to identify main environmental gradients and the variables that contribute the most to the total variance. Nitrate, phosphate, ammonium and electrical conductivity were identified as the most important water chemistry parameters, and typical vector-based spatial data analysis was applied to map their spatial distribution at sub-basin scale. In addition, we conducted simple linear models between the aforementioned parameters and the share of land uses within the basin of each sampling site in order to identify significant relationships. Agriculture was the most important land use affecting the nitrate and electrical conductivity, while artificial surfaces were the best predictor for phosphate and ammonium. Concerning the hydromorphological variability, fine types of substrate and discharge were the variables with the highest contribution to the total variance. Overall, the results of this article can be used for the preliminary assessment of susceptible areas/rivers to high levels of nutrient pollution that can aid water managers to formulate recommendations for improvement of further monitoring activities. Furthermore, our findings implicate the need for enhancement of agri-environmental measures and reduction of point-source pollution in disturbed areas to avert the risk of further environmental degradation under the anticipated global change.The implementation of the WFD relies on the measures proposed by the River Basin Management Plans (RBMPs) and the Programmes of Measures (PoMs) of river reconstruction, rehabilitation or restoration [4]. Quality elements for assessment are divided into biological, hydromorphological, and physicochemical, and for each one, a descriptive definition of high, good, moderate, poor, and bad status is given. Each National authority should set standards for those elements most relevant to the pressures faced by the water body under its responsibility and classify waters accordingly [2]. Across EU Member States discussions are on-going as to how to integrate climate change into the process of RBMPs for the next management cycles (2015-2027) of the WFD [1]. A key challenge in this context is the adaptation to climate change impacts through the design and implementation of PoMs at the river basin scale [5][6][7].Since the second WFD implementation cycle had ended in 2015 [8,9], several ...