Knowledge-based nitrogen (N) management provides better synchronization of crop N demand with N supply to enhance crop production while reducing N losses. Yet, how these N management practices contribute to reducing N losses globally is unclear. Here we compiled 5,448 paired observations from 336 publications representing 286 sites to assess the impacts of four common knowledge-based N management practices, including balanced fertilization, organic fertilization, co-application of synthetic and organic fertilizers, and nitrification inhibitors, on global ecosystem N cycling. We found that organic and balanced fertilization rather than N-only fertilization stimulated soil nitrate retention by enhancing microbial biomass, but also stimulated soil N leaching and emissions relative to no fertilizer addition. Nitrification inhibitors, however, stimulated soil ammonium retention and plant N uptake while reducing N leaching and emissions. Therefore, integrative application of knowledge-based N management practices is imperative to stimulate ecosystem N retention and minimize the risk of N loss globally.