Developed regions of the world represent a major atmospheric methane (CH4) source, but these regional emissions remain poorly constrained. The Yangtze River Delta (YRD) region of China is densely populated (about 16% of China’s total population) and consists of large anthropogenic and natural CH4sources. Here, atmospheric CH4concentrations measured at a 70-m tall tower in the YRD are combined with a scale factor Bayesian inverse (SFBI) modeling approach to constrain seasonal variations in CH4 emissions. Results indicate that in 2018 agricultural soils (AGS, rice production) were the main driver of seasonal variability in atmospheric CH4concentration. There was an underestimation of emissions from AGS in the a priori inventories (EDGAR—Emissions Database for Global Atmospheric Research v432 or v50), especially during the growing seasons. Posteriori CH4emissions from AGS accounted for 39% (4.58 Tg, EDGAR v432) to 47% (5.21 Tg, EDGAR v50) of the total CH4emissions. The posteriori natural emissions (including wetlands and water bodies) were 1.21 Tg and 1.06 Tg, accounting for 10.1% (EDGAR v432) and 9.5% (EDGAR v50) of total emissions in the YRD in 2018. Results show that the dominant factor for seasonal variations in atmospheric concentration in the YRD was AGS, followed by natural sources. In summer, AGS contributed 42% (EDGAR v432) to 64% (EDGAR v50) of the CH4concentration enhancement while natural sources only contributed about 10% (EDGAR v50) to 15% (EDGAR v432). In addition, the newer version of the EDGAR product (EDGAR v50) provided more reasonable seasonal distribution of CH4emissions from rice cultivation than the old version (EDGAR v432).