African mixed crop–livestock systems are vulnerable to climate change and need to adapt in order to improve productivity and sustain people’s livelihoods. These smallholder systems are characterized by high greenhouse gas emission rates, but could play a role in their mitigation. Although the impact of climate change is projected to be large, many uncertainties persist, in particular with respect to impacts on livestock and grazing components, whole-farm dynamics and heterogeneous farm populations. We summarize the current understanding on impacts and vulnerability and highlight key knowledge gaps for the separate system components and the mixed farming systems as a whole. Numerous adaptation and mitigation options exist for crop–livestock systems. We provide an overview by distinguishing risk management, diversification and sustainable intensification strategies, and by focusing on the contribution to the three pillars of climate-smart agriculture. Despite the potential solutions, smallholders face major constraints at various scales, including small farm sizes, the lack of response to the proposed measures and the multi-functionality of the livestock herd. Major institutional barriers include poor access to markets and relevant knowledge, land tenure insecurity and the common property status of most grazing resources. These limit the adoption potential and hence the potential impact on resilience and mitigation. In order to effectively inform decision-making, we therefore call for integrated, system-oriented impact assessments and a realistic consideration of the adoption constraints in smallholder systems. Building on agricultural system model development, integrated impact assessments and scenario analyses can inform the co-design and implementation of adaptation and mitigation strategies.F