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Due to the introduction of zero-till wheat in the Indo-Gangetic plains (IGP) in India, irrigation and fertilizer nitrogen (N) management needs to be modified from that followed under conventionally tilled fields. A field experiment was conducted to study the effect of irrigation and N levels on yield and N uptake by zero-till wheat, fertilizer N-use efficiency, and distribution of nitrate-N (NO3-N) in a soil profile under zero-till conditions in an acidic alluvial soil of the eastern IGP. The experiment was laid out in a split-plot design with four levels of irrigation as main plots (I0-no irrigation, rain-fed, I1-122 mm in one irrigation at 21 days after sowing (DAS), I2-263 mm in two irrigations at 21 and 42 DAS, and I3-386 mm in three irrigations at 21, 42, and 84 DAS) and 4 N levels [0 (N0), 60 (N1), 120 (N2), and 150 (N3) kg N ha−1] as subplots. Grain and straw yields were significantly higher at the irrigation level-I2 and 120 kg N ha−1-N2 over the control (I0 and N0) and were at par with the highest applied levels of irrigation and N (I3 and N3). The nitrogen uptake by wheat followed a trend similar to yield for irrigation levels; however, it increased significantly up to 150 kg N ha−1. After the harvest of wheat crop, more NO3-N was observed in the 60–90 cm subsurface soil layer than in the surface 0–15 cm and/or 15–30 cm and 30–60 cm subsurface soil layers. The highest NO3-N concentration was recorded in the treatment I2N2. Accumulation of NO3-N in the soil increased up to irrigation levels I2 and with increasing doses of fertilizer N application. Combined applications of irrigation and N had a positive and significant influence on agronomic efficiency (AE) and apparent N recovery (ANR) but had no significant effect on physiological efficiency (PE). This study suggests that an appropriate combination of irrigation and N levels in zero-till wheat can lead to not only high-yield levels and N-use efficiency but also adequately control NO3-N leaching under acidic alluvial soils in the eastern IGP.