The Small Sanjiang Plain (SSP), was formerly the largest wetland complex in China, located in the Northeastern part of Heilongjiang Province, China. Home to vast numbers of waterfowls, fish, and plants, the SSP is globally significant for biodiversity conservation. The loss and fragmentation of wetlands as a result agricultural development over 50 years has impacted wetland communities and their biodiversity. We used GIS to inventory large-scale land-use changes from 1950 to 2000, together with other statistical data. We found that 73.6% of the wetlands were lost due to agricultural development. Consequences of these land-use changes included: i) a rapid decline in waterfowl and plant species with the loss and fragmentation of natural wetlands and wetland ecosystem degradation; ii) greater variation in wetland water levels as the result of land-use changes over the years; iii) disruption of the dynamic river-floodplain connection by construction of drainage ditches and levees; and iv) a decrease in floodplain area that caused increased flooding peak flows and runoff. Here we show how these changes affect wetland biodiversity and impact important wetland species.