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Climate variability and changing cropping patterns are two main factors directly influencing catchment hydrological processes and agricultural productivity. Assessing the response of hydrological processes and agricultural production to the combined impacts is of great importance for enhancing water resources management, water productivity and agriculture sustainability. SWAT (Soil and Water Assessment Tools) models embedded with 2007 and 2018 land use were built for the San Joaquin watershed (SJWS) in California's Central Valley. Global sensitivity analysis were conducted to select parameters that have the largest influence on evapotranspiration (ET) processes. The model was calibrated and validated produced good agreement for monthly ET from remote sensing and yield of 8 major crops using county level reported yields during the periods of 2001–2009 and 2010–2018. Based on the outputs of the calibrated SJWS SWAT model, regional ET showed a significant increase, which was caused by rises in temperature and changing cropping patterns associated with increase in area under nut crop production. Seven major crop yields increased excluding alfalfa, implying that the impacts of increasing temperature and small decreases in precipitation were not dominant factors in explaining observed changes in yield. From periods 2001–2009–2010–2018, total water productivity (WP) increased slightly from 2.11 to 2.15 kg/m3, associated with more water-intensive permanent crop production systems. Total economic water productivity (EWP) increased significantly by 111% from 0.55 to 1.16 US$/m3, which also indicated the substantial economic benefit brought to the SJWS by expanding the land area under high-EWP crops such as nut crops and vegetables. Nutritional water productivity (NWP) for energy, protein and fat were reduced from 1211 kcal/m3, 183 g/m3 and 105 g/m3 to 1141 kcal/m3, 111 g/m3 and 88 g/m3 during the period 2010–2018 mostly due to high water use. Total NWP for calcium was increased from 114 to 145 mg/m3, respectively. This study provides initial insights into the response of WP, EWP and NWP to the changing cropping patterns and climate variability for major crops in the SJWS, which could be used by a wide range of stakeholders including farmers, commodity boards, irrigation districts, groundwater sustainability basins, environmental justice groups and policy makers to optimize water resources planning and management. We recommend creating a comprehensive index that incorporates WP, EWP and NWP for making sustainable water resources planning and management decisions. • Climate variability and cropping patterns change were analyzed from 1999 to 2018. • Regional evapotranspiration significantly increased over the past twenty years. • Total WP only increased slightly for the low WP of nut trees and its extended area. • Total EWP increased significantly by 111% from 0.55 to 1.16 US$/m3. • The paper also explores changes in NWP for various crops grown in the watershed. [ABSTRACT FROM AUTHOR]