The response of three durum wheat cultivars (C: Chen’s, V: Vitron, W: Waha) to irrigation was studied during 4 years in semi-arid Algeria (Chlef). The four treatments were NI (unirrigated), EI (early irrigation, up to heading), LI (late irrigation, from heading) and FI (full irrigation, over the entire season). FI increased rainfed grain yield (1,300 kg ha−1) by 270%, EI by 107%, and LI by 67%. The variety × irrigation interaction was significant each year. Under irrigation, cv. Vitron was generally the most productive cultivar while in rainfed conditions cv. Waha always resulted in the highest grain yield. Grain yield increased exponentially with seasonal evapotranspiration (r 2 = 0.741) and harvest index (r 2 = 0.873). Water use efficiency for grain ranged from 4.6–5.3 kg ha−1 mm−1 (NI) to 9.6–10.8 kg ha−1 mm−1 (FI) as a function of cultivar and irrigation, cv. Vitron and cv. Waha (full irrigation) and cv. Waha (rainfed) being the most efficient cultivars. According to the evaporation pan method, the seasonal crop coefficient (K c) values for the three cultivars were 0.64 (V), 0.62 (W) and 0.54 (C). The corresponding peak K c values were 1.0, 0.97 and 0.89, respectively. K c was closely related to leaf area index (LAI) and specific logarithmic relationships were calculated for each cultivar. Irrigation scheduling should be adapted to the type of cultivar in relation to its potential yield and LAI development pattern.