Soil degradation is a major problem for low land productivity in many parts of Ethiopia, including the Lake Tana basin. Understanding nutrient balances of different land uses help better understand nutrient depletion and thus sustainability of land productivity and the environmental wellbeing of an area. Nutrient balance analysis provides essential information concerning the current nutrient status of the soils and also used to take appropriate nutrient replenishment practices. Identification and measurement of nutrient input and output was conducted at Dera district, Northwestern Ethiopia in the cropping season of 2018 with the objective of identifying and measuring major nutrient inputs and outputs of different land uses. Participatory rural appraisal method, direct measurement and empirical formulas obtained from scientific research were used to investigate the movement of macronutrients specifically N, P and K in and out of the farm of different land use systems. Nutrient balances for NPK were analyzed based on four nutrient inputs/inflows and five nutrient outputs leaving the catchment. The results indicated that with the exception of phosphorus, teff cropland had negative partial N and K balances. The results also showed that the partial nutrient balances in wheat cropland were observed positive only for nitrogen (N). The full balances for the major cropland mainly wheat and teff were found to be -20.9 kg N, -0.7 kg P, -37.87 kg K ha-1 yr-1 and -61.4 kg N ,+11 kg P , and -26.7 kg K ha-1 yr-1 respectively. The full nutrient balances for the different land uses were -34 kg N , -0.27 kg P and -7.5 kg K ha-1 yr-1;for the rehabilitated land; -50.1kg N , +0.45kg P and -3.1kg K ha-1 yr-1 for grazing land; -48.6kg N ,-0.38kg P and -20.5kg K ha-1 yr-1for badland and-38.36kg N , +2.79kg P and -6.2kg K ha-1yr-1for natural forest. The share of nutrient loss through erosion was identified the highest path of nutrient depletion for all land uses. In general, negative N and K balances were found in this study for all land use. Therefore, the negative partial balances observed in cultivated land and other land uses indicated nutrient depletion which leads to land degradation and reduced agricultural productivity. Finally, analysis of the overall finding on nutrient balance implies that there is a need to sustain nutrient management at farm and watershed scale. Key Words: Nutrient input, nutrient output, nutrient balance, Lake Tana Basin