We used a process-based ecosystem model to examine methane (CH4) fluxes in the marshland across China as a result of multifactor global changes during 1949–2008. Our simulated results show a significant declining rate of 18.7 Gg Ca−1 (1Gg = 109 g) (with a 95% confidence boundary of 17.6 ∼ 19.8 Gg C a−1) at national scale, but substantially varying from the maximum annual CH4 emission of 2.4 Tg C a−1 (1Tg = 1012 g) (with a 95% confident boundary of 1.8 ∼ 3.4 Tg C a−1) in 1952 to the minimum annual CH4 emission of 1.3 Tg C a−1 (with a 95% confident boundary of 1.0 ∼ 1.9 Tg C a−1) in 2003. The marshland loss made the largest contribution to the CH4 emission reduction with an cumulative effect of 37.9 Tg C (with a 95% confident boundary of 28.0 ∼ 54.1 Tg C) for the past 60 years. Ozone pollution reduced CH4 emission, while elevated atmospheric CO2, nitrogen deposition, climate change, and multiple-factor interaction, cumulatively stimulated CH4emission. Climate variability predominately controlled the inter-annual variations in CH4 emissions. A substantial spatial variation in CH4 emission was observed across China's marshland. At regional scale, the Northeast, followed by Northwest and Southeast, made the greatest contribution, while North and Southwest made minor contributions to the national CH4 emission. This study suggests that it is necessary to consider multiple global change factors when estimating regional CH4 fluxes in natural wetlands.