Drainage and reduction in precipitation due to climate change have led to global declines in the water table (WT) of pristine peatlands, which have increased ecosystem releases of carbon dioxide (CO2) and nitrous oxide (N2O) and decreased emissions of methane (CH4). However, the trade-offs in these changes on net greenhouse gas (GHG) balances of peatlands globally remains unknown. Using meta-analysis and bootstrapped upscaling approaches, we assessed the global effect of WT decline on net GHG balances in peatlands, considering both on- and off-site (e.g., biomass removal, hydrological export, ditch emission) ecosystem fluxes of CO2, CH4 and N2O. We found that drainage caused a significant increase in net emissions of CO2 by 0.90 (95% confidence interval: 0.72–1.08) Pg CO2 yr–1 and of N2O by 0.09 (0.05–0.12) Pg CO2-eq. yr–1, while emissions of CH4 decreased by 0.30 (0.13–0.48) Pg CO2-eq. yr–1. The overall GHG balance significantly increased by 0.68 (0.43–0.94) Pg CO2-eq. yr–1. Climate, land use, and time since drainage introduced variability, with the conversion of (sub)tropical peatlands to agriculture and forestry dominating net global increases in peatland emissions (105%, range: 63–147%). In contrast, forestry in boreal peatlands reduced global GHG emissions by –4% (–8~–1%). Conversion of temperate and boreal peatlands to agriculture and forestry land uses was climate neutral overall, as increases in CO2 and N2O emissions were offset by reductions in CH4 emissions. Drained (sub)tropical peatlands for agriculture and forestry are global GHG emission hotspots. Conserving pristine peatlands and restoring degraded peatlands are needed particularly in the (sub)tropics for climate change mitigation.