Land-use change is one of the main indicators of soil quality. Soil physical and chemical properties vary with land use change and altitude as inferred from transect surveys and toposequences. Soil nitrogen, phosphorus, and potassium (NPK) are essential macronutrients for plant growth and soil nutrient balance. Their presence in the soil in appropriate quantities is important for maintaining crop yields and farmers income, particularly in developing countries where resources of soil chemical additives may be limited. This paper assesses the effects of land cover/use change and altitude on soil NPK nutrients in plots of 30 m2 in the North West Region of Cameroon for maintaining soil NPK levels and boosting crop yields. A total of 60 soil samples were collected at the 0-20 cm depth from the plots with various land cover/use types (eucalyptus plantation, farmland, grazing land, and natural forest). Soil samples were analyzed for nitrogen (N), phosphorus (P), and potassium (K) contents based on standard procedures. The concentrations of soil NPK nutrients were below the critical values for different land use types and the studied sites. The decline in soil NPK nutrient contents is partly linked to land use change, long-term nutrient mining through crop harvest, and rainfall-induced leaching of N and K nutrients. To increase food crop yields and sustain the livelihood of farmers, appropriate nature-based solutions of manure application, mulching, the intercropping of legumes, and sustainable use of appropriate chemical NPK fertilizers will help restore the soils and increase crop yields.