Rural development projects to develop sustainable agriculture need to be assessed before engaging smallholder farmers at large scale. Data on agricultural systems to produce food, provide income for smallholders and reduce greenhouse-gas (GHG) emissions are scarce in Sub-Saharan Africa countries. Here, we assessed the potential of agroecological practices (AP) on economic benefits to farmers, GHG balance derived from agricultural activities, and efficiency of economic investments to mitigate GHG. The study was based on a NGO rural development project, which promoted AP: agroforestry, compost, and System of Rice Intensification. The economic and GHG mitigation benefits were projected over a period of 20 years on three scenarios. Two scenarios, differing by two expected levels of AP adoption, were compared to a reference one, in which there was no NGO intervention. Socio-economic, yield and soil data were gathered on 192 farms during five growing seasons (2013–2018). The GHG balance was estimated with TropiC Farm Tool and EX-ACT. The GHG emissions were reduced in both scenarios compared to the reference one: −5.2 to −13.6 tCO2eq farm−1 yr−1 for scenario 1 and 2 respectively. At the regional scale, the projected amount of C saved per euro invested was estimated at −0.25 tCO2eq euro−1 and -0.41 tCO2eq Euro−1 (or € 4 to 2.5 tCO2eq−1) under scenario 1 and scenario 2. The annual cash flow of farmers increased over the 20 years. Our study highlighted the potential of AP for increasing productivity and profitability of smallholder agricultural systems for the Malagasy farmers, while simultaneously contributing to climate change mitigation.