This study evaluates the agrochemical consequences of irrigation erosion in meadow–serozem soils of the Zeravshan River Valley under tobacco cultivation. The influence of irrigation regime, slope position, and soil degradation on humus composition and nitrogen dynamics was investigated using field and isotope (^15N) experiments. Irrigation erosion significantly reduced soil fertility indicators in washed areas, where humus content in the 0–30 cm layer decreased to 0.8–1.0%, compared with 1.6–1.7% in non-eroded soils. Plant-available phosphorus ranged from 2.0–14.7 mg kg⁻¹ in eroded soils but increased to 7.6–27.0 mg kg⁻¹ in accumulated slope positions. Ammonium nitrogen reserves in the arable layer declined to 22.0–33.0 kg ha⁻¹ under erosion, whereas non-eroded soils contained 40.5–60.1 kg ha⁻¹. Application of a nitrification inhibitor increased fertilizer nitrogen use efficiency by tobacco plants from 32.5% to 46.6%, enhanced nitrogen fixation in soil from 21.4% to 29.3%, and reduced nitrogen losses through runoff and drainage water from 10.3% to 4.5%. Total nitrogen losses due to leaching and volatilization decreased from 35.8% to 19.6%. The results demonstrate that irrigation erosion substantially accelerates organic matter depletion and mineral nitrogen losses, while the use of nitrification inhibitors effectively improves nitrogen retention and nutrient-use efficiency, contributing to sustainable tobacco production on sloping irrigated lands.