In Egypt, wheat is the most consumed cereal grain, and its availability and affordability are important for social stability. Irrigation plays a vital role in wheat cultivation, despite intense competition for water resources from the River Nile across various societal sectors. To explore how grain and above-ground biomass yields respond to total seasonal water input from sowing to maturity in six bread wheat cultivars, eight field irrigation experiments were performed at four locations representative of three agro-climatic zones in two consecutive cropping seasons. A three-replicate strip-plot design was used with cultivars nested within the main plots featuring five irrigation treatments, ranging from six to two applications. Overall, irrigation treatment significantly affected nine agronomic traits. Compared with the six irrigation applications treatment (T1), the two irrigation applications treatment (T5) decreased the times to heading and maturity by 6.6 (7.3%) and 8.6 (6.3%) days, respectively. Similarly, T5 reduced the plant height by 14.9 cm (14.3%), flag leaf area by 12.0 cm² (27.2%), number of spikes per square metre by 77.7 (20.1%), number of kernels per spike by 13.9 (25.2%) and thousand grain weight by 10.0 g (19.6%). T5 also decreased the overall mean grain yield and above-ground biomass yield by 2834.9 (32.0%) and 7910.4 (32.86%) kg/ha, respectively. The grain yield and above-ground biomass production were consistently greater for all six cultivars at Al Mataenah and Sids than at Nubaria and Ismailia in the two cropping seasons. All six cultivars showed significantly greater responses to total seasonal water input for the grain yield and above-ground biomass at Al Mataenah and Ismailia. These results emphasise the necessity for choosing regions with favourable soil and climatic conditions to grow wheat cultivars that respond better to irrigation to enhance the large-scale production of wheat in Egypt. The grain and above-ground biomass yields were mostly linearly and positively associated with the total seasonal water input for all six cultivars at all four locations. This suggests that maintaining the current irrigation schedule of six irrigations is valid and should be practised to maximise productivity, particularly in areas similar to the three representative agro-climatic zones in Egypt.