No-tillage, plastic mulching, optimal irrigation, nutrient management, and crop rotation are valuable strategies for improving water use efficiency (WUE) in arid regions, but the effect of no-tillage combined with plastic mulching on WUE has not been tested. In 2016 and 2017, a field experiment was conducted after plastic mulched maize (Zea mays L.) in northwestern China to assess how tillage, irrigation, and nitrogen levels affect soil evaporation (E), evapotranspiration (ET), grain yield (GY), and WUE of wheat (Triticum aestivum L.). This study evaluated all combinations of two tillage practices (NT, no-tillage with previous plastic mulching; CT, conventional tillage), two irrigation levels (high: local conventional irrigation amount, 240 mm; and low: local conventional irrigation amount reduced by 20%, 192 mm), and three nitrogen levels (high: local conventional nitrogen amount, 225 kg ha−1; medium: local conventional nitrogen amount reduced by 20%, 180 kg ha−1; and low: local conventional nitrogen amount reduced by 40%, 135 kg ha−1). Across the study years, NT reduced E and E/ET and increased GY and WUE at all irrigation and nitrogen levels compared with CT. No-tillage with low irrigation and medium nitrogen reduced E, ET, and E/ET by 29%, 4%, and 26%, respectively, and improved GY and WUE by 19% and 24%, respectively, compared with CT with high supplies of irrigation and nitrogen. We concluded that NT into plastic mulched maize with a reduction in irrigation and a moderate level of nitrogen can improve WUE of wheat in arid regions, thereby enhancing the sustainability of cereal production.