Agricultural expansion and urban development without proper soil erosion control measures have become major environmental problems in Cambodia. Due to a high population growth rate and increased economic activities, land use and land cover (LULC) changes will cause environmental disturbances, particularly soil erosion. This research aimed to estimate total amounts of soil loss using the Revised Universal Soil Loss Equation (RUSLE) model within a Geographic Information System (GIS) environment. LULC maps of Japan International Cooperation Agency (JICA) 2002 and Mekong River Commission (MRC) 2015 were used to evaluate the impact of LULC on soil erosion loss in Stung Sangkae catchment. LULC dynamics for the study periods in Stung Sangkae catchment showed that the catchment experienced a rapid conversion of forests to paddy rice fields and other croplands. The results indicated that the average soil loss from the catchment was 3.1 and 7.6 t/ha/y for the 2002 and 2015 periods, respectively. The estimated total soil loss in the 2002 and 2015 periods was 1.9 million t/y and 4.5 million t/y, respectively. The soil erosion was accelerated by steep slopes combined with the high velocity and erosivity of stormwater runoff. The spatial distribution of soil loss showed that the highest value (14.3 to 62.9 t/ha/y) was recorded in the central, southwestern and upland parts of the catchment. It is recommended that priority should be given to erosion hot spot areas, and appropriate soil and water conservation practices should be adopted to restore degraded lands.