Abstract: Excessive N fertilizer application not only increases crop productivity, but also induces substantial environmental N losses that cause large environmental pollution risks. This study aimed to examine the effects of substituting synthetic N fertilizers with organic fertilizers on the reduction in environmental N losses from croplands in purple soil areas. Therefore, we conducted a one year field investigation to measure N-loss pathways and fluxes, crop productivity, and soil environmental variables in a wheat-maize rotation system under long-term different fertilization regimes with the same N rate, including the control (no fertilizer; NF); synthetic N fertilizer only (N); pig manure substituting 100% synthetic N fertilizer (pig manure; OM); regular synthetic N, P, and K fertilizer (NPK); combination of pig manure with synthetic N, P, and K fertilizer (OMNPK; pig manure substituting 30% synthetic N fertilizer); and combination of straw residue returned with synthetic N, P, and K fertilizer (CRNPK; straw residue substituting 15% synthetic N fertilizer). The results showed that N losses via surface runoff and sediment were in the range of 1.12–3.52 kg(N)∙hm⁻² and 1.48–7.26 kg(N)∙hm⁻², respectively. The N leaching losses via interflow ranged from 12.53 to 76.72 kg(N)∙hm⁻², which were over 10 times greater than those for surface runoff; nevertheless, N leaching losses accounted for 90.6% of the total hydrological N losses. These results indicate that N leaching via interflow is the predominant pathway of hydrological N losses, thereby highlighting that sloping cropland of purple soil is one of the hotspots of N leaching losses from agricultural soils in China. Compared with that of the NPK treatment, the substitution of synthetic N fertilizer with organic fertilizers (OM, OMNPK, and CRNPK treatments) decreased the total hydrological N losses by 32.1%, 27.5%, and 21.2%, respectively. This was mainly because practices with substitution of synthetic N fertilizer with organic fertilizers significantly decreased N leaching losses via interflow compared with the application of synthetic N fertilizer only. Furthermore, considering the crop yields, the substitution of synthetic N fertilizer with organic fertilizer treatments (OM, OMNPK, and CRNPK treatments) significantly increased the total annual crop yields by 23.0%, 17.8%, and 4.1%, respectively, and decreased the yield-scaled total hydrological N losses by 24.3% to 44.8%. Therefore, the long-term substitution of synthetic N fertilizer with organic fertilizer can not only increase the crop productivity of both wheat and maize, but also decrease environmental N losses, thereby decreasing the risk of agricultural non-point source pollution in the purple soil region. Overall, the substitution of synthetic N fertilizer with organic fertilizers can be recommended as an optimized agricultural N management strategy to reduce synthetic N fertilizer rates and improve N use efficiency in agricultural systems of the purple soil region.