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Given the current scarcity of freshwater resources, it is imperative to explore new agricultural management options to sustainably enhance food production. Desalinated seawater (DSW) presents a promising solution for irrigation in water-stressed regions. However, its application in perennial crops has been poorly assessed, potentially posing challenges to existing cultivation practices due to higher associated costs, salinity, and the presence of potentially harmful elements, notably boron (B). To address these uncertainties, a three-year experiment was conducted to evaluate the short-term effects of irrigation with DSW on a ‘Rio Red’ grapefruit orchard. Four irrigation treatments were assessed: DSW, freshwater (FW), a 1:1 mixture of DSW and FW (MW), and DSW with reduced B concentration (DSW–B). At present, the young age of the trees (3.5 years) and their grafting onto a five-year-old rootstock at the beginning of the experiment likely facilitated rapid foliar mass development and prevented the accumulation of phytotoxic elements up to critical levels. However, local DSW consistently exceeded recommended citrus thresholds for B (0.5 mg L–1), sodium (Na+; 115 mg L–1), and chloride (Cl–; 250 mg L–1) in irrigation water, resulting in significant concentrations of B (2.1 mg kg–1), Na+ (504 mg L–1) and Cl– (476 mg L–1) in soil. Moreover, these levels led to concentrations in leaves close to defined thresholds in the case of Na+ (0.25 g 100 g–1), and exceeded them in the case of B (>250 mg kg–1). Although fruit quality remained unaffected, variability in yield among trees and the cost disparity between water resources, resulted in slight fluctuations in the income-outcome balance during initial cultivation years. Our findings offer insights into the irrigation of sensitive crops with DSW, aimed at mitigating potential soil and plant harm from early accumulation of phytotoxic elements. Further research is warranted to explore the impact of both single and sustained DSW usage for irrigation purposes.