Assessing how livelihoods in rural sub-Saharan Africa might change given future trends in socio-economic and biophysical conditions helps to identify and direct effective efforts towards poverty reduction. Based on existing literature, hypothetical changes in farmer practices and policy interventions were described and used to build five contrasting scenarios towards the year 2027. A simulation framework was developed to assess food self-sufficiency and income per capita now and in the future for a representative village of 99 households in Southern Mali. In the current situation, 26% of the farms were food self-sufficient and above the 1.9 US$ day-1 poverty line. This percentage would fall to 13% in the “Business as usual” scenario. In the “Dairy development” scenario, with intensification of livestock production and support to the milk sector, 27% of farms would be food self-sufficient and non-poor. Additional policy interventions targeting family planning and job creation outside agriculture would be needed to improve both household food self-sufficiency and income per capita. In this optimistic scenario, 77% of the farms would be non-poor and food self-sufficient in 2027. Additional programs to promote Integrated Pest Management, small-scale mechanization and mineral fertilizer on traditional cereals could allow a drastic increase in productivity and would lift 94% of the farm population out of poverty. Considering the entire heterogeneous farm population was crucial to accurately assess pathways out of poverty. Our study stresses the need for a strategic and multi-sectoral combination of interventions to improve livelihoods.