The Upper Brahmaputra River Basin is prone to natural disasters and environmental stresses (floods, droughts and bank erosion, delayed rainfall, among others) creating an environment of uncertainty and setting the basin back in terms of socio-economic development. The climate change literature shows that agriculture and ecosystems and their services are highly climate sensitive, yet they are the main sources of livelihood that supports a large proportion of residents of the tributaries of the Brahmaputra River Basin. The continuous depletion of ecosystems and loss of agricultural outputs resulting from environmental stressors has a substantial impact on the socio-economic wellbeing of the basins residents, particularly the vulnerable rural poor. This paper uses spatially explicit data from Census, Household Surveys and Earth Observation to develop a transferable methodological approach which investigates the extent of dependence on agriculture and ecosystems as a source of livelihood in the contrasting sub-basins of the Brahmaputra River in the State of Assam, India and Bhutan, and the risk to these livelihood dependencies in these sub-basins due to potential environmental impacts of climate change. The results from this study constitute a case study in the development of a systematic and spatially explicit set of tools that inform and assist policy makers in the appropriate interventions to secure the livelihood benefits of sustainably managed agriculture in the face of environmental change.