As one of the most important food crops, the potato is widely planted in the oasis agricultural region of Northwest China. To ascertain the impact of regulated deficit irrigation (RDI) on various facets including dry matter accumulation, tuber yield, quality and water use efficiency (WUE) of potato plants, a two-growth season field experiment under mulched drip irrigation was conducted in the desert oasis region of Northwest China. Water deficits, applied at the seedling, tuber formation, tuber expansion and starch accumulation stages, encompassed two distinctive levels: mild (55-65% of field capacity, FC) and moderate (45-55% FC) deficit, with full irrigation (65-75% FC) throughout the growing season as the control (CK). The results showed that water deficit significantly reduced (p < 0.05) above-ground dry matter, water consumption and tuber yield compared to CK, and the reduction increased with the increasing water deficit. A mild water deficit at the tuber formation stage, without significantly reducing (p > 0.05) yield, could significantly increase WUE and irrigation water use efficiency (IWUE), with two-year average increases of 25.55% and 32.33%, respectively, compared to CK. Water deficit at the tuber formation stage increased starch content, whereas water deficit at tuber expansion stage significantly reduced starch, protein and reducing sugar content. Additionally, a comprehensive evaluation showed that a mild water deficit at the tuber formation stage is the optimal RDI strategy for potato production, providing a good balance between yield, quality and WUE. The results of this study can provide theoretical support for efficient and sustainable potato production in the desert oasis regions of Northwest China.