Effective water and fertilizer management is crucial for enhancing nitrogen (N) use efficiency and ensuring regional food security, especially in arid regions. Drip fertigation can synchronize water and fertilizer supply with crop demand, but its maximum benefits can only be achieved with appropriately designed and well-managed irrigation systems. In this study, we built on our previous work on optimizing the design of drip irrigation systems and evaluated the effect of drip fertigation regimes on soil nitrate nitrogen (NO3-N) supply, crop N uptake, yield, and yield stability. We conducted a five-year field experiment using drip fertigation to grow maize (Zea mays L.) in the Hetao Irrigation District, Northwest China, from 2016 to 2020. We implemented three water levels by controlling soil matric potential (SMP) threshold values [− 10 kPa (S1), − 30 kPa (S3), and − 50 kPa (S5)] under the same N fertilization rate (150 kg N ha−1 broadcast as basal fertilizer, 150 kg N ha−1 applied with drip fertigation). Our results indicated that soil NO3-N in 0–60 cm profile was typically distributed in the non-mulched zone at maturity. Compared with S5, S1 and S3 on average significantly decreased NO3-N accumulation in the 0–60 cm profile by 66% and 47%, and S1 and S3 significantly decreased NO3-N accumulation in the 60–120 cm profile by 31% and 30%. In addition, the S3 significantly decreased NO3-N accumulation in the 120–200 cm profile by 52% and 35% compared with S1 and S5. S3 significantly improved crop grain yield by 45%, sustainable yield index by 26%, N uptake by 28%, and N utilization efficiency by 11% compared with S5. In contrast, S3 decreased the irrigation amount by 40% compared with S1, with no significant differences in grain yield, yield stability, and N uptake in most years. We recommend using an SMP threshold value of − 30 kPa combined with a drip fertigation rate of 150 kg N ha−1 to reduce residual NO3-N and improve yield and yield stability in arid regions. Furthermore, we also recommend using drip fertigation with 208–253 mm irrigation water in wet years and > 253 mm in dry years (irrigation every four days from V6 to R3 stage), with 13.6 kg ha−1 N applied per irrigation (from VT to R3 stage) to facilitate farmer operations. Our research provides valuable technical guidance to promote a stable and sustainable agricultural production in arid regions.