This study was conducted in the Roodasht region of Isfahan, Iran, during 2019 and 2020 to investigate the effects of irrigation regimes on quinoa grain yield and water use efficiency (WUE). The experiment was arranged in a randomized complete block design with three treatments and three replications, comprising nine experimental plots. The irrigation treatments (T1, T2, and T3) consisted of soil moisture depletion levels of 30%, 50%, and 70%, respectively, during the mid-growth stage, while irrigation was triggered at 30% soil moisture depletion during the other growth stages. The results showed that irrigation treatments had significant effects on grain yield, biomass yield, and WUE at the 1% significance level (P < 0.01), and on thousand-kernel weight at the 5% significance level (P < 0.05). Mean comparisons using Duncan’s multiple range test at the 5% significance level indicated that T1 produced the highest mean grain yield (2,220 kg ha-1), followed by T2 (1,440 kg ha-1) and T3 (880 kg ha-1). Across both years, soil moisture depletion levels of 50% and 70% during the mid-growth stage reduced grain yield by 39% and 66%, respectively, compared with the control treatment (T1). The highest WUE values were also obtained under T1, reaching 0.82 in the first year and 0.61 in the second year.