The upstream Dong Nai River Basin is located in the country’s key economic development region and its water resources are a key component of sustainable regional development. The objective of this study was to assess the impact of land use and land cover changes (LULCC) on the flow regime in this tropical forest basin using a flow–duration curve analysis that has been widely used in Japan. This study combined two different temporal and spatial scales of satellite data, Landsat and Global Inventory Modeling, and Mapping Studies (GIMMS) normalized difference vegetation index (NDVI) to analyze LUCC. Results from the land cover classification of five Landsat images between 1973 and 2014 indicated that the forest area decreased significantly in the period of 1994 to 2005 due to population growth, leading to land conversion for agriculture. Furthermore, secular changes in the annual GIMMS-NDVI data revealed that land cover changes occurred from 1996 and a large amount of forest was lost in 1999; however, due to the rapid regrowth of secondary forest of tropical forests and the development of the crop, the vegetation recovered shortly afterwards in 2000 before decreasing again after 2004. Following large-scale deforestation, the total discharge, maximum flow, and the plentiful, ordinary, low, and small-scale runoff increased sharply and decreased thereafter because of vegetation regrowth.