In areas where water is scarce, the use of regulated deficit irrigation, combined with decision support system tools, may decrease the impact of agriculture on natural water resources, as well as on energy consumption, thereby improving the profitability of farms. With this aim, the SUBSTOR-Potato model (incorporated in the DSSAT Program) was evaluated with a 2-year field test (2011 and 2012) conducted in a semi-arid area (Albacete, Spain) applying four irrigation levels (120, 100, 80 and 60% of irrigation requirements). Subsequently, the model was used for simulating the potato yield under several deficit irrigation strategies (ISs) during 30 years of a semi-arid climate (1988–2017) and determining the most profitable option. The considered ISs were deemed those most suitable from the yield and water productivity point of view by some authors. The model performance for tuber yield was satisfactory with an index of agreement >0.91 and errors between 0.71 and 3.06 × 103 kg/ha. The ISs simulated with SUBSTOR-Potato showed that slight deficit irrigation (5–10%) may increase the water productivity and profitability of the farms. Moreover, tuber formation (from onset of tuber initiation to harvest) was shown to be the most sensitive stage, therefore it is highly recommended to avoid deficit during this stage, which would cause a large reduction in yield (around 8 t/ha, depending on the level of deficit suffered by the crop).