This study estimates the effect of climate change on water resources efficiency and crop/agronomic productivity at the coastal agricultural Almyros basin, in Greece. Groundwater resources in the studied basin are intensively mined for irrigation, whereas their quantity and quality are highly downgraded. Multi-model climate projections for Representative Concentration Pathways (RCPs 4.5 and 8.5) from the Med-CORDEX database for precipitation and temperature have been used to evaluate the impacts of climate change on the studied area. The multi-model climate projections have been bias-corrected with Quantile Empirical Mapping. Simulation of coastal water resources has been performed using a calibrated Integrated Modelling System (IMS) consisting of coupled and interconnected models of surface hydrology (UTHBAL), groundwater hydrology (MODFLOW), nitrate leaching/crop growth (REPIC), nitrate pollution (MT3DMS), and seawater intrusion (SEAWAT) for the historical period of 1991–2018, and the projected future period 2019-2100. Analysis of the simulation results for the various water resources management and crop/agronomic scenarios have been evaluated using the Standardized Chloride Hazard Index (SCHI), the Crop Water Productivity (CWP) index for crop yields and irrigation water, the Nitrogen Use Efficiency (NUE) index, and the Economic Water Productivity (EWP) index for the gross profits of irrigation water, based on historical and projected growth ratios until 2100. The results indicate how the various water resources development, and the agronomic scenarios will affect the water use and agricultural production management and help to develop adaptive and sustainable agricultural and water resources management plans under climate change.