Drip irrigation systems are becoming more and more mature and are now widely used to improve crop yield and nitrogen use efficiency in Xinjiang, NW China. However, it is not known if leaching is occurring or not and whether leaching will harm the water environment following N fertilization and drip irrigation. The purpose of our study was to estimate the leaching volumes, nitrogen losses, forms of nitrogen losses, and nitrogen loss coefficients under different N fertilization, P fertilization, K fertilization and irrigation regimes. A long-term field experiment was conducted from 2009 to 2015 in Baotou Lake farm in Korla City, Xinjiang, with drip-irrigated cotton (Gossypium hirsutum L.) being grown under different N fertilizer and irrigation regimes. The treatments were designed comprising 0 N, 0 P, and 0 K with an irrigation of 480 mm as the control(N0P0K0W480) and the following three other treatments: (1) 357 kg N·hm−2, 90 kg P·hm−2, 0 kg K2O hm−2, and irrigation of 480 mm (N357P90K0W480); (2) 357 kg N·hm−2, 90 kg P·hm−2, 62 kg K·hm−2, and irrigation of 420 mm (N357P90K62W420); and (3) 240 kg N·hm−2, 65 kg P·hm−2, 62 kg K·hm−2, and irrigation of 420 mm (N240P65K62W420). The results showed the following: (1) the leaching volume was determined by nitrogen fertilization, phosphorus fertilization, and the irrigation amount. In general, the leaching volume was highest under treatment N357P90K0W480. (2) The nitrogen loss was highest under treatment N357P90K0W480. (3) Nitrate nitrogen (NO3–) was the main form of nitrogen lost, followed by ammonium nitrogen (NH4+). (4) The annual nitrogen loss coefficients followed the order of: N357P90K0W480 > N357P90K62W420 > N240P65K62W420 > N0P0K0W480, with values of 0.85, 0.55, 0.30, and 0, respectively. The leaching volume, nitrogen loss, nitrate nitrogen, ammonium nitrogen, and annual nitrogen loss coefficient were lowest under the N240P65K62W420 treatment, except in the N0P0K0W480treatment. These results demonstrate that optimizing the management of water and nitrogen (N240P65K62W420 treatment) can effectively reduce nitrogen losses under drip fertigation and plastic mulching.