Wastewater treatment plants (WWTPs) contribute to anthropogenic greenhouse gas (GHG) emissions. Due to the lack of estimation methods and operation data, whole plant characterization of GHG emissions from WWTPs is still unclear. In this study, a set of methods were developed to calculate direct, indirect and avoided GHG generated from large-scale WWTPs in China. The characteristic of GHG emissions from two representative large-scale WWTPs situated in eastern China were investigated. Results showed that the GHG emission of sludge treatment and disposal from two WWTPs accounted for 76% and 65% of total emissions, respectively. This study investigated the GHG performance of three typical sludge treatment and disposal routes including land application (R1), incineration (R2) and landfilling (R3). R3 showed the highest GHG emission with 4322 kg CO2-eq/t dry sludge, followed by R2 (3124 kg CO2-eq/t dry sludge) and R1 (489 kg CO2-eq/t dry sludge). Two energy recovery strategies were evaluated in terms of their impacts on the GHG emissions from R1, R2 and R3. Strategy A and B reduced significantly GHG emission from three routes. R3 exhibited the best performance of GHG reduction with reduction rate of 51% (strategy A) and 77% (strategy B). The future direction of CO2 emission reduction is to minimize landfill disposal of sludge and to utilize sludge as a source of energy.