Water shortage and soil degradation are major challenges to agricultural production encountered in the semi-arid areas. The advantage of application of organic and biofertilizers in improving the soil productivity have been verified. However, there is still a lack of related research evaluating the effect of integrated fertilization measures on soil quality and crop productivity as well as their potential relationships under varying water supply levels. Herein, a two-year field study with two water levels (sufficient water, 220 mm; limited water, 60 mm) and five fertilization treatments (CK, no fertilizer; CF, chemical fertilizer; CFB, bio-fertilizer combined with CF; CFO, organic fertilizer combined with 70 % CF; CFOB, bio-fertilizer combined with CFO) was conducted to evaluate the effects on grain yield, resource use efficiency and soil quality. The results showed that the limited water supply decreased the grain yield, dry matter weight, nitrogen (N) uptake, N use efficiency, water productivity and most soil properties compared with those under sufficient water supply. Among different fertilization measures, CFOB was superior to other treatments both at sufficient and limited water supply, as it significantly improved the maize average yield (2022 and 2023), dry matter weight, N uptake, NUE and WP by 18.2-27.3 %, 9.2-31.2 %, 13.3-16.6 %, 38.9-62.3 %, 18.7-26.8 % compared with CF, respectively. Moreover, CFOB promoted the soil quality index (SQI) by improving the soil properties and consequently increased the grain yield. Accordingly, the integrated application of biofertilizer, organic and chemical fertilizer would be a sustainable fertilization strategy for improving soil quality and crop productivity, particularly in the semiarid sandy areas. Additionally, the results also revealed the underlying mechanisms of positive response between grain yield and SQI under varying water supply levels, which mainly attributing to the different key soil factors related to the grain yield. This study provided theoretical guidance for fertilization measures under varying water supply to improve soil quality and sustainable development of agriculture.