Under changing climate, water scarcity and frequent incidence of diseases like stripe rust pose the biggest threat to sustainable crop production which jeopardizes nutritional security. A study was executed to rationalize crop water requirement and evaluate wheat (Triticum aestivum L. cv. Bohoth 3) yield losses by stripe rust infection under irrigated conditions. Seven water treatments included three irrigations in three stages/season (S 3), four irrigations (S 4), and five irrigations (S 5) at the different sensitive growth stages, full (F), and two deficit irrigation levels including D 1 = 80% of field capacity (FC) and D 2 = 70% (FC) along with farmers’ practice of irrigation as control (C). Results revealed that F and D 1 boosted grain yield by 31 and 14%. Overall, F irrigation regime resulted in the highest grain production (2.93 ton/ha) as well as biomass yield (13.2 ton/ha). However, D 2 had the highest value of grain protein (15.9%) and achieved the highest application efficiency (AE) at midseason (54.6%) and end season (59.6%), and the lowest AE was under S 3. Also, halting irrigation at the milky stage (S 5) led to a significant decrease in irrigation water use efficiency as compared to D 1. However, cutting irrigation at the end of seedling, heading, and milky stages (S 3) caused a significant reduction in E a, crop water use (ETa), and 1000 grain weight in comparison with all other treatments. Regarding yellow rust, S 3 irrigation regime resulted in the lowest incidence of yellow rust infection. The highest irrigation and water use efficiency values were recorded under D 1 (0.79 and 0.59 kg/m3), and the lowest values were obtained for control. Hence, the deficit irrigation treatment D 1 could be recommended as the best appropriate strategy to save more water and to improve the water productivity under Yemeni agroclimatic conditions.