Assessing the impacts of different land uses on soil physicochemical properties is a fundamental step towards sustainable land management. This study was conducted in Agedit watershed, northwest Ethiopia with the objective of determining the effects of land use and soil depth on soil physicochemical properties. Three major land use types: natural forest, grazing and cultivated lands were selected while soil samples were collected in the 0-20 and 20-40cm depths. Standard soil analytical procedures were followed in carrying out soil analysis. Statistical analysis revealed notable variations due to differences in land use type and soil depth. Sand and clay particles, bulk density, total porosity, pH, organic matter, total nitrogen, available phosphorus, cation exchange capacity and exchangeable K and Na were significantly affected (p ≤ 0.05 and/or p ≤ 0.01) by land use. In contrast, silt, particle density, carbon to nitrogen ratios, exchangeable Ca, and Mg and PBS were not significantly (p > 0.05) affected. With soil depth, higher mean values of total nitrogen, organic matter, exchangeable K and pH were recorded in the 0-20 cm than in the 20-40 cm depth. A shift from forest to other land use types caused a significant decline on soil fertility parameters which contributed to low agricultural productivity. The study area, therefore, needs immediate intervention to protect the remnant forests and to replenish the degraded soil properties for sustainable agricultural productivity.