Small- and medium-scale cocoa farmers are severely affected by the impacts of climate change as the sector is bedeviled by other challenges such as soil degradation, pests, diseases, and poor yields coupled with poor agronomic practices. Climate-smart agricultural technologies and practices thus offer a way to addressing the sector’s challenges and adaptation to the adverse impacts of climate change. This chapter explores the potential of climate-smart agriculture vis-à-vis conventional cocoa farming systems to enhance production and build resilience, in addition to understanding key challenges influencing the application of climate-smart agriculture technologies and practices. Using a quantitative research methods approach, data was collected in the Sankore Cocoa District in Ghana’s Ahafo region through semi-structured household questionnaires. The analyses focused on key variables such as educational levels, farm/land tenure, age of farmers, location of farm, residential status, and access to extension services as some of the main determining factors influencing the application of climate-smart agricultural practices among cocoa farmers in Ghana. The findings revealed that an in-depth understanding of these variables can help ascertain ways to strengthen climate-smart agricultural strategies in the cocoa sector as well as their contributions to building resilience.