AbstractRapid climate change and intensified human activities have resulted in water table lowering (WTL) and enhanced nitrogen (N) deposition in Tibetan alpine wetlands. These changes may alter the magnitude and direction of greenhouse gas (GHG) emissions, affecting the climate impact of these fragile ecosystems. We conducted a mesocosm experiment combined with a metagenomics approach (GeoChip 5.0) to elucidate the effects of WTL (−20 cm relative to control) and N deposition (30 kg N ha−1 yr−1) on carbon dioxide (CO2), methane (CH4) and nitrous oxide (N2O) fluxes as well as the underlying mechanisms. Our results showed that WTL reduced CH4 emissions by 57.4% averaged over three growing seasons compared with no‐WTL plots, but had no significant effect on net CO2 uptake or N2O flux. N deposition increased net CO2 uptake by 25.2% in comparison with no‐N deposition plots and turned the mesocosms from N2O sinks to N2O sources, but had little influence on CH4 emissions. The interactions between WTL and N deposition were not detected in all GHG emissions. As a result, WTL and N deposition both reduced the global warming potential (GWP) of growing season GHG budgets on a 100‐year time horizon, but via different mechanisms. WTL reduced GWP from 337.3 to −480.1 g CO2‐eq m−2 mostly because of decreased CH4 emissions, while N deposition reduced GWP from 21.0 to −163.8 g CO2‐eq m−2, mainly owing to increased net CO2 uptake. GeoChip analysis revealed that decreased CH4 production potential, rather than increased CH4 oxidation potential, may lead to the reduction in net CH4 emissions, and decreased nitrification potential and increased denitrification potential affected N2O fluxes under WTL conditions. Our study highlights the importance of microbial mechanisms in regulating ecosystem‐scale GHG responses to environmental changes.