Ghana’s Western North and Central Regions are biodiversity-rich landscapes. Cocoa is a major commodity produced in these two regions, accounting for over 50% of Ghana’s cocoa output. As part of the efforts to further improve productivity and ecological health of the landscape, the Government of Ghana initiated the Cocoa Disease and Pests Control Programme primarily to control cocoa pests and diseases, including the use of pesticides. In recent times, however, there has been an upsurge in the use of highly hazardous pesticides (HHPs) that have far-reaching consequences on human and ecological health of the cocoa production landscape. To gain a better understanding of pesticide-use patterns on cocoa farms and address HHP-driven biodiversity loss, Conservation Alliance International (CA) conducted a study within the landscape. The study was based on both qualitative and quantitative research approaches to understand pesticide use and resulting impacts on human and ecological health. In all, 306 cocoa farmers were surveyed. Analysis of the data revealed that about 81% of the cocoa farmers use pesticides to address pests and diseases, causing visible impacts on humans and the environment, including skin irritation, eye irritation, and death of pollinators. Pesticide use was exacerbated by the adverse economic impacts of the COVID-19 pandemic. Policymakers are therefore advised to take steps to phase out HHPs, promote integrated pest management, and tackle the spread of COVID-19 infections.