Climate change is threatening food systems and agriculture in sub-Saharan Africa. Smallholder farmers are struggling to adapt to extreme weather events associated with climate variability and need substantial support to feed rapidly growing populations. Climate-smart agriculture (CSA) has the potential to play a significant part in achieving climate resilience, adaptation and sustainable agriculture. Nevertheless, there are various social, institutional, environmental and economic barriers impeding the widespread adoption of CSA practices and approaches in the African region. A nuanced understanding of these barriers and their impact on the adoption of CSA practices is crucial for transforming Africa’s agriculture. This paper seeks to explore the most common and most significant barriers impeding the upscaling of CSA practices in sub-Saharan Africa and to highlight the actions needed to remove these impediments and promote the introduction of widespread CSA practices across the region.