Mekong River Delta, is located at the southern of Vietnam, covers a large area that is approximately 40,000 square kilometers. Its surrounding coastline comprises of the east part and the west part. The east coastline lengthens from Ho Chi Minh City to Ca Mau headland (South China Sea), while the west coastline distributes from Ca Mau headland to Ha Tien town (Thailand Gulf). Most of areas are low plains with mean altitude ranged from less than 0.5 meter to approximately 10 meters. These areas are sensitive with the rising of the global mean sea level in present and future times. To gain a better understanding of this vulnerable area and make a good plan for the future, it is crucial to observe and calculate the erosional and depositional areas, as well as to study the coastline changes from past to present time. In this research, we use multi-temporal Landsat imagery acquired from 1972 to 2005 to detect the coastline from each image. Comparing the derived coastlines enables us to observe and calculate the areas of erosion and deposition in each stage. Landsat imagery with 30 meters resolution is provided free by NASA that is appropriated for observing in a large area such as Mekong River Delta. The result is useful for studying the changing rates and the factors of the erosion and deposition in Mekong river delta. This research also provides the useful information for land-use planning, as well as warning and finding out methods to overcome the consequence of rising sea level in future.