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Water and fertilizer play an important role in crop growth in dryland areas. It is a necessity to improve the water use efficiency (WUE) of the crop once the water resource is limited. In northern China, where there is a wide shortage of water resources, it is therefore necessary to investigate how fertilization affects the WUE of spring maize and to quantify the effects. A total of 33 published peer-reviewed papers were collected, and a meta-analysis and random forest model analysis were performed with 364 WUE comparisons, aiming to explore the effects of fertilization on the WUE of spring maize and to clarify the optimal conditions for WUE under fertilizer management. The results showed that fertilization significantly increased the WUE of spring maize by 56.72% (P < 0.01) when compared with non-fertilization. The WUE effect under the organic–inorganic fertilizer combination (MNPK) was approximately twice as high as that under inorganic fertilizer (NPK) or organic fertilizer (M). The greatest increase in WUE occurred at 0–100 kg ha−1 of nitrogen application (NA). Under environmental conditions including 7 ≤ mean annual temperature in the test year (T) ≤ 10 °C, 400 ≤ mean annual precipitation in the test year (P) ≤ 600 mm, and mean altitude (A) > 1500 m, and soil conditions including 10 ≤ soil organic matter content (SOM) ≤ 14 g kg−1 and available phosphorus (AP) < 5 mg kg−1, the fertilization optimally enhanced the WUE of spring maize when the agronomic measures of ridge–furrow planting (RFP) and mulching film (MF) were used. The random forest model analysis indicated that the influence factors (i.e., fertilizer regimes, environmental factors, soil factors, and agronomic measures) caused 65.62% of the variation in spring maize WUE effects, while in all influence factors, fertilizer types related to fertilizer regimes caused the most variation. The initial available potassium (AK) and available nitrogen (AN) of the soil were negatively correlated to the WUE effect, indicating that fertilization imposed a better effect on the WUE of spring maize when the soil was infertile. Fertilization significantly increased the WUE of spring maize, and organic and inorganic fertilizer application provided an effective measure for the sustainable development of spring maize in northern China. After clarifying the required conditions for fertilization increasing WUE, high-efficiency water use may be achieved. [ABSTRACT FROM AUTHOR]