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Because of inadequate water resources and poor irrigation facilities, salinity and drought stresses often co-occur in rice production in saline lands. Nevertheless, little information is available on the agro-physiological traits and grain yield of rice when subjected to combined salinity × drought stress. We evaluated the individual and interactive influences of salinity and drought on rice yield and agro-physiological characteristics using two rice cultivars, Nanjing 9108 (salinity-tolerant rice) and Wuyunjing 30 (salinity-susceptible rice). This experiment was conducted under non-salinity (NS) and salinity (S) conditions and three drought levels from jointing to heading (CC, control condition; MD, moderate drought; SD, severe drought). Individual salinity and drought treatments and their combination shortened the total growth duration by 3–4 days and 4–6 days in Nanjing 9108 and Wuyunjing 30, respectively. Both salinity and drought treatments reduced (P < 0.01 or P < 0.05) rice yield by 12.9%−40.9% and 28.1%−35.0% across the two cultivars, respectively, and the combined salinity × drought treatment resulted in a more pronounced yield loss of 53.1%−113.3%. A greater reduction in grain yield caused by the combined salinity × drought stress was detected in Wuyunjing 30 than in Nanjing 9108. The poor grain yield performance of rice under combined salinity × drought stress was mainly attributable to the following: (1) yield components, panicle length, and single panicle weight were lower than they were under an individual stress; (2) combined stress caused greater reductions in shoot biomass, leaf area index (LAI), and nonstructural carbohydrate (NSC) content in the stem at heading and maturity, although harvest index and NSC remobilization reserve were increased; (3) each stress and especially combined stress increased Na+/K+ ratio in the leaf, while reducing leaf photosynthetic rate and SPAD values after heading, and total accumulation of nitrogen (N), phosphorus (P), and potassium (K). Our results suggested that the combined salinity × drought stress was more damaging than either stress alone, and resulted in a greater yield penalty of rice. In terms of grain yield, salinity-susceptible rice was more responsive to the combined stress than salinity-tolerant rice. • The effects of combined salinity × drought stress on rice yield and NPK uptake were evaluated. • The combined salinity × drought stress reduced rice yield more than either stress alone. • Salinity-susceptible rice was more responsive to the combined salinity × drought stress. [ABSTRACT FROM AUTHOR]