Potential evapotranspiration (ET₀) is a fundamental component of the water cycle and is highly sensitive to climate change. In this study, the Hargreaves-Samani (HS) method was calibrated regionally for Iran for the first time, using observational data from 152 synoptic stations during the baseline period 1995–2014 against the FAO56 Penman-Monteith reference method. Four calibration approaches (daily and monthly scales, including linear and second-order fits) were evaluated on the aggregated data of six climatic-altitudinal zones. The monthly linear method showed the highest performance, with a mean R² of 0.89 and a mean RMSE of 0.77 mm day⁻¹, and was selected as the most suitable option. Consequently, correction coefficients were derived for the six zones and applied to estimate future ET₀ (2030–2090) using outputs from three CMIP6 models (ACCESS-CM2, IPSL-CM6A-LR, and CNRM-CM6-1) under three emission scenarios (SSP1-2.6, SSP2-4.5, SSP5-8.5). Results indicate an increasing trend of ET₀ across all regions of Iran, with average increases during the far future period (2071–2090) ranging from 58% to 129% relative to the baseline. The highest sensitivity is observed in high-latitude low-altitude zones and dry central areas, while mountainous regions show the smallest increases. The largest absolute increases occur in summer months (up to 15.5 mm month⁻¹), whereas the largest relative increases occur in winter (up to 182%). These findings provide a serious warning for future water stress in the agricultural sector and underscore the urgent need to revise cropping patterns—particularly in central arid regions during summer—and to adopt climate-adaptive water management strategies.