Soil fertility depletion in smallholder farms is one of the fundamental biophysical causes for declining per capita food production in Ethiopia. In the present study, we assess soil nutrient depletion and its spatial variability for Ethiopia and its regional states, using nutrient balances as a tool. Data on crop production, fertilizer use and land management practices were collected from the Agricultural sample survey, which was carried out by the Central Statistics Authority (CSA) for the production year 1999/2000. We used a Geographic Information System (GIS) to process, and analyze spatially referenced information like soil properties, precipitation and land use types. We calculated nutrient balances for N, P and K from five nutrient fluxes entering and five nutrient fluxes leaving cultivated lands of smallholders. Some of the fluxes (e.g. leaching, denitrification and wet deposition) were estimated using transfer functions. Erosion was estimated by universal soil loss equation (USLE) and landscape process modelling at multi-dimensions and scales (LAPSUS). At the national level, full nutrient balance results indicate a depletion rate of 122 kg N ha-1 yr-1, 13 kg P ha-1 yr-1 and 82 kg K ha-1 yr-1. Soil nutrient stocks in all regional states were decreasing with the exception of areas under permanent and vegetable crops. In the analysis, soil erosion was the major cause for nutrients depletion, but this flux shows significant variability between different estimates and was highly uncertain. We calculated that the contribution of erosion to N losses was 70%, while its contribution to P and K losses were 80% and 63%, respectively. Nutrient losses under permanent and vegetable cropping were caused mainly by residues removal, harvested products and leaching, while losses under cereals and other annuals were dominated by erosion.