Inhibitors are widely considered an efficient tool for reducing nitrogen (N) loss and improving N use efficiency, but their effectiveness is highly variable across agroecosystems. In this study, we synthesized 182 studies (222 sites) worldwide to evaluate the impacts of inhibitors (urease inhibitors [UI], nitrification inhibitors [NI] and combined inhibitors) on crop yields and gaseous N loss (ammonia [NH₃] and nitrous oxide [N₂O] emissions) and explored their responses to different management and environmental factors including inhibitor application timing, fertilization regime, cropping system, water management, soil properties and climatic conditions using subgroup meta‐analysis, meta‐regression and multivariate analyses. The UI were most effective in enhancing crop yields (by 5%) and reducing NH₃ volatilization (by 51%), whereas NI were most effective at reducing N₂O emissions (by 49%). The application of UI mitigates NH₃ loss and increases crop yields especially in high NH₃‐N loss scenarios, whereas NI application would minimize the net N₂O emissions and the resultant environmental impacts especially in low NH₃‐N loss scenarios. Alternatively, the combined application of UI and NI enables producers to balance crop production and environmental conservation goals without pollution tradeoffs. The inhibitor efficacy for decreasing gaseous N loss was dependent upon soil and climatic conditions and management practices. Notably, both meta‐regression and multivariate analyses suggest that inhibitors provide a greater opportunity for reducing fertilizer N inputs in high‐N‐surplus systems and presumably favor crop yield enhancement under soil N deficiency situations. The pursuit of an improved understanding of the interactions between plant‐soil‐climate‐management systems and different types of inhibitors should continue to optimize the effectiveness of inhibitors for reducing environmental losses while increasing productivity.