A 2-year study was conducted to determine the response of four sunflower cultivars (Master, Lakumka, Favorite and Berezanski) to different irrigation regimes: 45 (control), 60, 75 and 90% (I1–I4) of maximum allowable depletion (MAD) of available soil water (ASW). Severe deficit irrigation (I3 and I4) significantly decreased water-use efficiency, radiation use efficiency, yield and yield-related components. The results also showed that water deficit, compared to full-irrigated treatment (I1), increased the activity of all antioxidant enzymes in leaves. Master had the highest seed yield in full and limited irrigation as well as the highest antioxidant enzymes content. Sunflower plants extracted most of the soil moisture from 0 to 50 cm soil layer. Therefore, it is recommended that only the 0–50 cm soil profile be considered for scheduling irrigation. Measured and simulated results revealed a special irrigation regime threshold for each cultivar with respect to seed yield. The response rate to irrigation regime ceased in higher irrigation rates as I join (65, 63, 65 and 70% MAD for Master, Lakumka, Favorite and Berezanski, respectively). Moreover, all estimated I join for all cultivars were higher than the current recommendation of 50% MAD. This shows the ability to sustain the yield of these sunflower cultivars in the study region under deficit irrigation. The seed yield of all four cultivars tended to respond similarly to irrigation in both years, but Master was more efficient than the remaining three cultivars with respect to the response to diverse treatments.