Most nitrogen (N) applied to plants as fertilizer is lost through leaching. Here, nanocellulose was used in mitigating N leaching loss. Lettuce-cropped soil was treated with unmodified or Zn-modified nanocellulose (1–2% by wt) in combination with NPK, compared with urea and NPK-only treatments. Consecutive leaching, plant growth, plant N uptake, and soil nitrogen retention were assessed. Nanocellulose + NPK significantly (p ≤ 0.05) reduced N leaching, compared with urea and NPK-only. 1-and-2 wt % nanocellulose, as well as Zn-modified 1-and-2 wt % nanocellulose, reduced N leaching by 45, 38, 39, and 49% compared with urea and by 43, 36, 37, and 47% compared with NPK-only, respectively. Nitrogen leached mainly as NO3– (98.4%). Compared with urea and NPK, lettuce shoot mass was significantly (p ≤ 0.05) increased by 30–42% and by 44–57%, respectively, by all nanocellulose treatments, except for the Zn-modified 1 wt % nanocellulose. Leached N negatively correlated to biomass yield. Soil N retention was enhanced by the pristine and Zn-modified nanocelluloses between 27 and 94%. Demonstrably, nanocellulose can be utilized for mitigating N loss in soil and supporting crop production, resource management, and environmental sustainability.