Water-table drawdown across peatlands increases carbon dioxide (CO2) and reduces methane (CH4) emissions. The net climatic effect remains unclear. Based on global observations from 130 sites, we found a positive (warming) net climate effect of water-table drawdown. Using a machine-learning-based upscaling approach, we predict that peatland water-table drawdown driven by climate drying and human activities will increase CO2 emissions by 1.13 (95% interval: 0.88–1.50) Gt yr−1 and reduce CH4 by 0.26 (0.14–0.52) GtCO2-eq yr−1, resulting in a net increase of greenhouse gas of 0.86 (0.36–1.36) GtCO2-eq yr−1 by the end of the twenty-first century under the RCP8.5 climate scenario. This drops to 0.73 (0.2–1.2) GtCO2-eq yr−1 under RCP2.6. Our results point to an urgent need to preserve pristine and rehabilitate drained peatlands to decelerate the positive feedback among water-table drawdown, increased greenhouse gas emissions and climate warming. The climate impact of water-table drawdown in peatlands is unclear as carbon dioxide emissions increase and methane emissions decrease due to drying. This study shows decreasing water-table depth results in net greenhouse gas emissions from global peatlands, despite reducing methane emissions.