In the middle reaches of the Heihe River basin, environmental deterioration in agricultural ecosystems caused by excessive nitrogen (N) supply and high irrigation rate has received much attention in recent years. A field experiment was designed to investigate the effects of different irrigation and N supply levels on soil NO-3-N accumulation and distribution, grain yield, N uptake and N use efficiency in a recently reclaimed sandy farmland system in the Heihe River basin. The experiment followed a completely random split-plot design, taking the irrigation treatment as main-plot (with three levels of 378, 504 mm, and 630 mm for the whole growing season) and N supply treatment as split-plot (with four levels of 0, 140, 221, 300 kg hm-2; denoting Ｎ0, Ｎ140, Ｎ221, andＮ300, respectively). Our results showed that grain yields, above-ground dry-matter biomass, plant N in above-ground dry-matter biomass, apparent N recovery fraction, and physiological efficiency did not increase significantly with increasing N supply rates when N supply rate exceeded 221 kg hm-2. Average grain yields in Ｎ221 were found to be 46.7%, 41.3% and 9.5% higher than Ｎ0, Ｎ140 and Ｎ300, respectively, whereas average above-ground dry-matter biomasses in Ｎ221 were 31.3%, 25.2% and 3.5% higher than Ｎ0, Ｎ140 and Ｎ300, respectively. Under the rates of irrigation between 378 mm and 504 mm, a rate of N supply over 221 kg hm-2 resulted in a significant accumulation of NO-3-N (from 50 kg hm-2 to 140 kg hm-2) in the 0-200 cm soil profile. Under the rate of irrigation of 630 mm, NO-3-N accumulation in the 0-200 cm soil profile ranged from 25 kg hm-2 to 47 kg hm-2 at harvest stage, being lower than that (58 kg hm-2 to 63 kg hm-2) at sowing. Overall, N fertilizer productivity varied from 6.3 kg kg-1 to 10.8 kg kg-1, while irrigation water productivity varied from 2.0 kg hm-2 mm-1 to 5.3 kg hm-2 mm-1 in this recently reclaimed sandy farmland system. However, we found that neither irrigation nor nitrogen supply had a significant influence on soil water storage. The results of this study suggest that the combination of irrigation and nitrogen supply of 378 mm and 221 kg N hm-2 may be the best management strategy because of its relatively higher grain yield, higher irrigation water productivity, and higher N use efficiency, as well as lower NO-3-N accumulation.