Enhanced efficiency nitrogen fertilizers (EENFs), including nitrification inhibitors (NIs) and slow-release fertilizers (SRFs), are considered a feasible pathway for improving grain yield and mitigating greenhouse gas (GHG) emissions. However, the usage of EENFs in an intensified spring wheat system has not been well documented. The combined application of EENFs with water and fertilizer management (EENFs-WFM) was investigated in an irrigated spring wheat cropping system over two years. Measurements of soil nitrous oxide (N2O), methane (CH4) and carbon dioxide (CO2) fluxes were taken across five treatments: no N fertilizer as a control (CK), conventional N fertilization and irrigation (Con), optimum N fertilization and irrigation (Opt), optimum N fertilization and irrigation plus nitrification inhibitor (Opt + NI), and optimum N fertilization as slow-release fertilizer and irrigation (Opt-SRF). The cumulative N2O emissions in both growing seasons were significantly (P < 0.05) higher than the fallow seasons and accounted for 56–83% of total emissions. The Opt, Opt-SRF, and Opt + NI treatments significantly reduced the cumulative N2O emissions by 25%, 34%, and 45%, respectively, relative to the Con treatment, while the fertilizer N input decreased by 36%. The soil acted as a tiny sink for atmospheric CH4, with no significant effect in any treatment. Moreover, global warming potential (GWP) and greenhouse gas intensity (GHGI) declined by ∼45% and ∼33%, respectively, in the Opt + NI treatment and ∼46% and ∼34%, respectively, in the Opt-SRF treatment, relative to the Con treatment, with almost no effect on grain yield. Our results highlight that EENFs-WFM is a promising management system for maintaining yield while minimizing GWP and GHGI.