The intensification of wetland landscape fragmentation has seriously affected the protection of wetland biodiversity and the maintenance of wetland ecosystem service functions. This study took the Suaeda salsa wetland in the Liaohe River Estuary as the research object, and constructed the wetland landscape database from 1985 to 2019 based on the GIS platform, quantitative analysis of wetland landscape fragmentation characteristics and its driving factors. The results showed that from 1985 to 2019, the Suaeda salsa wetland in the Liaohe River Estuary showed a degrading trend, which was manifested in the shrinkage of wetland area and increased fragmentation of wetland landscape. The area of Suaeda salsa wetland reached its maximum of 4, 158.81 hectares in 1988, and the degree of landscape aggregation was relatively high. After that, the wetland landscape fragmentation first increased, then decreased and finally increased. Suaeda salsa wetland landscape fragmentation in 2003 and 2019 was the most serious, with fragmentation degrees reaching 5.90 and 7.89, respectively; the main driving factors affecting the landscape fragmentation of Suaeda salsa wetland in the Liaohe River Estuary were man-made development activities and hydrological processes; the overall upward trend of landscape fragmentation was related to road construction and farmland development. There was a good spatial correspondence between aquaculture, runoff and sediment transport. Road construction, farmland development, increase of aquaculture area, and reduction of runoff and sediment transport were the main factors leading to the fragmentation of the Suaeda salsa wetland landscape.