In Africa, climate change will result in disruptions in temperature, atmospheric CO2 content and rainfall, with impacts on cotton cultivation, particularly in terms of yield, precocity and resistance to pests and diseases. To adapt to these disruptions and mitigate their negative impacts, the implementation of modified or innovative sustainable cotton-based cropping systems must contribute to the conservation of resources and biodiversity. For this purpose, several ways are possible. The first way concerns sustainable land management, by mobilizing processes of ecological intensification of cropping and production systems: land development, restoring fallow land, participatory mapping or installation of firewalls, to frame biomass fluxes at territory level. The second way concerns the management of soil organic matter, with effects on water retention, erosion or nutrient availability: increase soil carbon storage, in particular through the International 4 per 1,000 Initiative. The third way concerns the agro-ecological management of pests and diseases: use of farming practices such as mulch, no tillage, and preservation of functional biodiversity. The fourth way concerns the varietal component of the cropping system: selection of varieties that are early, compact, and resilient to disturbance effects. In conclusion, Africa faces specific constraints related to climate change but also has opportunities for adaptation and mitigation, both at the technical and political levels.