Rapid development in the upper reaches of the Mekong River, in the form of construction of large hydropower dams and reservoirs, large irrigation schemes, and rapid urban development, is putting water resources under stress. Recent studies have concluded that these developments will lead to flow alterations in the Mekong River. These flow alterations would threaten the sensitive ecosystems downstream, particularly Tonle Sap River, Tonle Sap Lake, its floodplain, and its gallery forest and protected areas, by changing the flood-pulse system of the lake. This article estimates the changes in parameters of the Tonle Sap flood pulse due to the aforementioned flow alterations. The impacts on the flooded area and loss of gallery forest and protected areas were analyzed using geographic information system-based methods. Relatively small rises in the dry-season lake water level would permanently inundate disproportionately large areas of floodplain, rendering it inaccessible to floodplain vegetation and eroding the productivity basis of the ecosystem. It is highly important to maintain the natural hydrological pattern of the Mekong River, particularly the dry-season water levels, to preserve Tonle Sap Lake's ecosystem productivity.