||Smallholder agriculture in sub-Saharan Africa provides basis of rural livelihoods and food security, yet farmers have to cope with land constraints, variable rainfall and unstable institutional support. This study integrates a diversity of approaches (household typology and understanding of farm trajectories, on-farm trials, participatory ex-ante trade-off analysis) to design innovative farming systems to confront these challenges. We explored farm trajectories during two decades (1994 to 2010) in the Koutiala district in southern Mali, an area experiencing the land constraints that exert pressure in many other parts of sub-Saharan Africa. We classified farms into four types differing in land and labour productivity and food self-sufficiency status. During the past two decades, 17% of the farms stepped up to a farm type with greater productivity, while 70% of the farms remained in the same type, and only 13% of the farms experienced deteriorating farming conditions. Crop yields did not change significantly over time for any farm type and labour productivity decreased. Together with 132 farmers in the Koutiala district, we tested a range of options for sustainable intensification, including intensification of cereal (maize and sorghum) and legume (groundnut, soyabean and cowpea) sole crops and cereal-legume intercropping over three years and cropping seasons (2012-2014) through onfarm trials. Experiments were located across three soil types that farmers identified – namely black, sandy and gravelly soils. Enhanced agronomic performance was achieved when targeting legumes to a given soil type and/or place in the rotation: the biomass production of the cowpea fodder variety was doubled on black soils compared with gravelly soils and the additive maize/cowpea intercropping option after cotton or maize resulted in no maize grain penalty, and 1.38 t ha−1 more cowpea fodder production compared with sole maize. Farm systems were redesigned together with the farmers involved in the trials. A cyclical learning model combining the on-farm testing and participatory ex-ante analysis was used during four years (2012-2015). In the first cycle of 2012-2014, farmers were disappointed by the results of the ex-ante trade-off analysis, i.e marginal improvement in gross margin when replacing sorghum with soybean and food self-sufficiency trade-offs when intercropping maize with cowpea. In a second cycle in 2014-2015 the farm systems were re-designed using the niche-specific (soil type/previous crop combinations) information on yield and gross margin, which solved the concerns voiced by farmers during the first cycle. Farmers highlighted the saliency of the niches and the re-designed farm systems that increased farm gross margin by 9 to 29% (depending on farm type and options considered) without compromising food self-sufficiency. The involvement of farmers in the co-learning cycles allowed establishment of legitimate, credible and salient farm reconfiguration guidelines that could be scaled-out to other communities within the “old cotton basin”. Five medium-term contrasting socio-economic scenarios were built towards the year 2027, including hypothetical trends in policy interventions and change towards agricultural intensification. A simulation framework was built to account for household demographic dynamics and crop/livestock production variability. In the current situation, 45% of the 99 households of the study village were food self-sufficient and above the 1.25 US$ day-1 poverty line. Without change in farmer practices and additional policy intervention, only 16% of the farms would be both food self-sufficient and above the poverty line in 2027. In the case of diversification with legumes combined with intensification of livestock production and support to the milk sector, 27% of farms would be food self-sufficient and above the poverty line. Additional broader policy interventions to favour out-migration would be needed to lift 69% of the farms out of poverty. Other additional subsidies to favour yield gap narrowing of the main crops would lift 92% of the farm population out of poverty. Whilst sustainable intensification of farming clearly has a key role to play in ensuring food self-sufficiency, and is of great interest to local farmers, in the face of increasing population pressure other approaches are required to address rural poverty. These require strategic and multi-sectoral approaches that address employment within and beyond agriculture, in both rural and urban areas.