Changes in land cover (LC) can lead to environmental challenges, but few studies have investigated LC changes at a country wide scale in Ghana. Tracking LC changes at such a scale overtime is relevant for devising solutions to emerging issues. This study examined LC changes in Ghana for the past almost two and half decades covering 1995–2019 to highlight significant changes and opportunities for sustainable development. The study used land cover data for six selected years (1995, 2000, 2005, 2010, 2015, and 2019) obtained from the European Space Agency. The data was analyzed using R, ArcGIS Pro and Microsoft Excel 365 ProPlus. The original data was reclassified into eight LC categories, namely: agriculture, bare area, built-up, forest, grassland, other vegetation, waterbody, and wetland. On average, the results revealed 0.7%, 131.7%, 23.3%, 46.9%, and 11.2% increases for agriculture, built-up, forest, waterbody, and wetland, respectively, across the nation. However, losses were observed for bare area (92.8%), grassland (51.1%), and other vegetation (41%) LCs overall. Notably, agricultural land use increased up to 2015 and decreased subsequently but this did not affect production of the major staple foods. These findings reveal the importance of LC monitoring and the need for strategic efforts to address the causes of undesirable change.