Connections between social drivers (human activities) and ecological drivers (natural events) are currently considered as the key factors affecting land use change in tropical wetland ecosystem. However, the complexity interaction of these socio-ecological drivers is often poorly understood. This paper examined the interaction of these two systems in the Kilombero valley floodplain. Kilombero valley floodplain is one of the largest tropical wetland in Africa offering a wide spectrum of habitats for plant and animal species sustaining several ecosystem services and ecological functions, which has been under threat of wetland loss and degradation. The study used the documentary review approach to investigate the interaction of socio and ecological systems in the study area. The study revealed that population growth, market growth and price incentive for cash crops and timber products coupled with improved infrastructures, policy and institutional framework are the social drivers, while flat terrain characteristics, heavy black alluvial soils coupled with high water holding capacity, increased temperature and rainfall variability accompanied with prolonged dry spells are the ecological drivers of land use change and wetland conversion in the study area. However, there are relationships among these drivers, as they act simultaneously as well as differently to influence land use changes in the study area. The study recommended that socio-ecological interactions and the needs of local communities whose livelihood is highly dependent on wetland resources must be central to the development of wetland policies and wetland management approaches.