The change in Ethiopia’s economic policy from small scale farming to large scale farming began with the global food and fuel crisis in 2007/8. This has led many countries including the Gulf States and several East Asian countries, to re-evaluate their strategies and secure land and water essentially to produce food and fuel. Consequently, in Ethiopia, more than four million hectares of land has been leased to investors for large-scale commercial farming out of which the total land area of 524,202.58 hectares has been distributed for both local and foreign investors in Gambella Regional State. Hence, the main purpose of the study was to assess the impacts of large-scale commercial farming on the sustainability of environment in Gambella regional state. To this end both primary and secondary data sources were utilized. The study found that, though the large-scale commercial farming is contributing to the economy both at national and regional level, it has adverse impacts on the environment. To mention a few, the unconstitutional procedure followed in land transfer, investors’ undue concern and care for natural resources, and the absence of guidelines and frameworks endanger the environment. In addition, the absence of synergy among actors contributed towards drastic environmental problems. Besides, the study found that the investment in the region is disconnecting the environment from its dependents (local people) and putting the sustainability of the environment in a query unless it is managed with immediate interventions by the concerned bodies.