This study evaluates the interaction effect of different irrigation strategies and winter wheat cultivars on yield and water use efficiency in a semi-arid region. The aim is to identify effective water-saving strategies for sustainable winter wheat production considering the variability in annual rainfall patterns over two years in Shiraz, Iran. The irrigation strategies included full irrigation (FI), deficit irrigation at 0.75FI, 0.5FI, and rainfed with supplemental irrigation at sowing. Two winter wheat cultivars, Varedati and Sirvan, were tested. The results showed no significant differences in grain yield, dry matter, and harvest index between the two cultivars. However, deficit irrigation (0.75FI and 0.5FI) and rainfed conditions led to a significant reduction in winter wheat yield and dry matter. The first year, with lower rainfall, resulted in a 16% decrease in grain yield and dry matter compared to the second year with higher rainfall. The rainfed treatment, supplemented with irrigation at sowing, yielded about 44% of the full irrigation regime in both years. Deficit irrigation negatively impacted yield components such as 1000-grain weight and the number of spikes per unit area. The Varedati cultivar had lower 1000-grain weight and spikes per unit area but a higher number of grains per spike compared to the Sirvan cultivar. In comparison to FI, rainfed treatments decreased RLD by 45% in both years. However, Sirvan cultivar exhibited a higher level of resistance in terms of root growth under water stress conditions.The study highlights the importance of selecting suitable irrigation strategies based on annual rainfall patterns to optimize winter wheat yield and water use efficiency in semi-arid regions.