Technical options in crop and animal husbandry to reduce soil nutrient mining and other forms of natural resource degradation in the Sudano-Sahelian zone should be economically attractive, if they are to be adopted. A model is presented in which agronomic and economic information and goals are combined to explore possibilities for agro-ecologically sustainable and economically viable land use in three different climatic regions in Mali and for a situation of non-degraded soils. The time frame of the study is to the year 2010. For each region, an agro-ecologically sustainable land use system (a combination of crop, livestock and pasture production systems) that maximizes income of the agricultural sector and satisfies self sufficiency targets is identified. Special attention is given to the use of chemical fertilizer in crop activities. It is shown that use of chemical fertilizer is an important element of sustainable and economically viable land use, especially in higher rainfall regions. Population size has a marked effect on optimal land use systems in the regions, but self sufficiency is not endangered even if the population is 50% higher than estimated for 2010. It is argued that results should not be used to simulate the actual situation or future developments, but to define priorities for agricultural development in the Sudano-Sahelian region.