Human activities have rapidly accelerated global nitrogen (N) cycling since the late 19th century. This acceleration has manifold impacts on ecosystem N and carbon (C) cycles, and thus on emissions of the greenhouse gases nitrous oxide (N2O), carbon dioxide (CO2), and methane (CH4), which contribute to climate change. First, elevated N use in agriculture leads to increased direct N2O emissions. Second, it leads to emissions of ammonia (NH3), nitric oxide (NO), and nitrogen dioxide (NO2) and leaching of nitrate (NO3−), which cause indirect N2O emissions from soils and waterbodies. Third, N use in agriculture may also cause changes in CO2 exchange (emission or uptake) in agricultural soils due to N fertilization (direct effect) and in non-agricultural soils due to atmospheric NHx (NH3+NH4) deposition (indirect effect). Fourth, NOx (NO+NO2) emissions from combustion processes and from fertilized soils lead to elevated NOy (NOx+ other oxidized N) deposition, further affecting CO2 exchange. As most (semi-) natural terrestrial ecosystems and aquatic ecosystems are N limited, human-induced atmospheric N deposition usually increases net primary production (NPP) and thus stimulates C sequestration. NOx emissions, however, also induce tropospheric ozone (O3) formation, and elevated O3 concentrations can lead to a reduction of NPP and plant C sequestration. The impacts of human N fixation on soil CH4 exchange are insignificant compared to the impacts on N2O and CO2 exchange (emissions or uptake). Ignoring shorter lived components and related feedbacks, the net impact of human N fixation on climate thus mainly depends on the magnitude of the cooling effect of CO2 uptake as compared to the magnitude of the warming effect of (direct and indirect) N2O emissions. The estimated impact of human N fixation on N2O emission is 8.0 (7.0–9.0) Tg N2O-N yr−1, which is equal 1.02 (0.89–1.15) Pg CO2-C equivalents (eq) yr−1. The estimated CO2 uptake due to N inputs to terrestrial, freshwater, and marine ecosystems equals −0.75 (−0.56 to −0.97) Pg CO2-C eq yr−1. At present, the impact of human N fixation on increased CO2 sequestration thus largely (on average near 75%) compensates the stimulating effect on N2O emissions. In the long term, however, effects on ecosystem CO2 sequestration are likely to diminish due to growth limitations by other nutrients such as phosphorus. Furthermore, N-induced O3 exposure reduces CO2 uptake, causing a net C loss at 0.14 (0.07–0.21) Pg CO2-C eq yr−1. Consequently, human N fixation causes an overall increase in net greenhouse gas emissions from global ecosystems, which is estimated at 0.41 (−0.01–0.80) Pg CO2-C eq yr−1. Even when considering all uncertainties, it is likely that human N inputs lead to a net increase in global greenhouse gas emissions. These estimates are based on most recent science and modeling approaches with respect to: (i) N inputs to various ecosystems, including NH3 and NOx emission estimates and related atmospheric N (NH3 and NOx) deposition and O3 exposure; (ii) N2O emissions in response to N inputs; and (iii) carbon exchange in responses to N inputs (C–N response) and O3 exposure (C–O3 response), focusing on the global scale. Apart from presenting the current knowledge, this article also gives an overview of changes in the estimates of those fluxes and C–N response factors over time, including debates on C–N responses in literature, the uncertainties in the various estimates, and the potential for improving them.