Anaerobic oxidation of methane (AOM) in wetland soils is widely recognized as a key sink for the greenhouse gas methane (CH). The occurrence of this reaction is influenced by several factors, but the exact process and related mechanism of this reaction remain unclear, due to the complex interactions between multiple influencing factors in nature. Therefore, we investigated how environmental and microbial factors affect AOM in wetlands using laboratory incubation methods combined with molecular biology techniques. The results showed that wetland AOM was associated with a variety of environmental factors and microbial factors. The environmental factors include such as vegetation, depth, hydrogen ion concentration (pH), oxidation-reduction potential (ORP), electrical conductivity (EC), total nitrogen (TN), nitrate (NO), sulfate (SO), and nitrous oxide (NO) flux, among them, soil N substances (TN, NO, NO) have essential regulatory roles in the AOM process, while NO and NO may be the key electron acceptors driving the AOM process under the coexistence of multiple electron acceptors. Moreover, denitrification communities (narG, nirS, nirK, nosZI, nosZII) and anaerobic methanotrophic (ANME-2d) were identified as important functional microorganisms affecting the AOM process, which is largely regulated by the former. In the environmental context of growing global anthropogenic N inputs to wetlands, these findings imply that N cycle-mediated AOM processes are a more important CH sink for controlling global climate change. This studying contributes to the knowledge and prediction of wetland CH biogeochemical cycling and provides a microbial ecology viewpoint on the AOM response to global environmental change.