Worldwide, scarce water resources and substantial food demands require efficient water use and high yield. This study investigated whether irrigation frequency can be used to adjust soil moisture to increase grain yield and water use efficiency (WUE) of high-yield maize under conditions of mulching and drip irrigation. A field experiment was conducted using three irrigation intervals in 2016: 6, 9, and 12 days (labeled D6, D9, and D12) and five irrigation intervals in 2017: 3, 6, 9, 12, and 15 days (D3, D6, D9, D12, and D15). In Xinjiang, an optimal irrigation quota is 540 mm for high-yield maize. The D3, D6, D9, D12, and D15 irrigation intervals gave grain yields of 19.7, 19.1–21.0, 18.8–20.0, 18.2–19.2, and 17.2 Mg ha⁻¹ and a WUE of 2.48, 2.53–2.80, 2.47–2.63, 2.34–2.45, and 2.08 kg m⁻³, respectively. Treatment D6 led to the highest soil water storage, but evapotranspiration and soil-water evaporation were lower than other treatments. These results show that irrigation interval D6 can help maintain a favorable soil-moisture environment in the upper-60-cm soil layer, reduce soil-water evaporation and evapotranspiration, and produce the highest yield and WUE. In this arid region and in other regions with similar soil and climate conditions, a similar irrigation interval would thus be beneficial for adjusting soil moisture to increase maize yield and WUE under conditions of mulching and drip irrigation.