Greenhouse gas (GHG)-induced climate change is among the most pressing sustainability challenges facing humanity today, posing serious risks for ecosystem health. Methane (CH4) and nitrous oxide (N2O) are the two most important GHGs after carbon dioxide (CO2), but their regional and global budgets are not well known. In this study, we applied a process-based coupled biogeochemical model to concurrently estimate the magnitude and spatial and temporal patterns of CH4 and N2O fluxes as driven by multiple environmental changes, including climate variability, rising atmospheric CO2, increasing nitrogen deposition, tropospheric ozone pollution, land use change, and nitrogen fertilizer use. The estimated CH4 and N2O emissions from global land ecosystems during 1981–2010 were 144.39 ± 12.90 Tg C/yr (mean ± 2 SE; 1 Tg = 1012 g) and 12.52 ± 0.74 Tg N/yr, respectively. Our simulations indicated a significant (P < 0.01) annually increasing trend for CH4 (0.43 ± 0.06 Tg C/yr) and N2O (0.14 ± 0.02 Tg N/yr) in the study period. CH4 and N2O emissions increased significantly in most climatic zones and continents, especially in the tropical regions and Asia. The most rapid increase in CH4 emission was found in natural wetlands and rice fields due to increased rice cultivation area and climate warming. N2O emission increased substantially in all the biome types and the largest increase occurred in upland crops due to increasing air temperature and nitrogen fertilizer use. Clearly, the three major GHGs (CH4, N2O, and CO2) should be simultaneously considered when evaluating if a policy is effective to mitigate climate change.