Ecological grief is an emerging mental health concern and is projected to increase as climatic stressors worsen. Climate change and variability pose significant threats to the mental health of smallholder farmers residing in harsh ecological zones in Sub-Saharan Africa that rely solely on rain-fed agriculture. These farmers experience feelings of grief, despair, distress, and uncertainty related to climate-change-induced ecological losses. As extreme climate change events increase in intensity and frequency and reinforce existing vulnerabilities, such as poverty and poor health, climate-induced ecological grief will worsen among smallholder farmers due to their low adaptive capacities and resilience. Yet, ecological grief is largely unexplored within a Sub-Saharan African context as most studies have concentrated on high-income countries. Using data from semi-structured interviews with farmers (n = 60), we examine ecological grief among smallholder farmers in the harshest agro-ecological zone of Ghana in the context of a rapidly changing climate and agrarian regime. Our findings indicate a range of climate-related contexts in which ecological grief has been reported, including grief associated with physical ecological losses and grief attributed to loss of environmental knowledge, eroding culture and tradition, rising insecurity, and perceived emasculations. Additionally, we find gender differences in the triggers of ecological grief between men and women. This paper recommends that environmental policies should include measures that support farmers’ mental health as climate change stressors worsen in agrarian areas.