Forests provide immeasurable merits for the economies of most developing countries. Forests in developing countries experience harmful human-induced impacts such as unregulated removal of biodiversity and unsustainable land conversion. The Sefwi Wiawso District (SWD) located in Ghana, which includes portions of six protected forest reserves (FRs) such as Muro, Tano Suhien, Tano Suraw, Suhuma, Sui River, and Krokosua, is the subject of this study. The impacts of selected spatial variables on forest losses were examined using retrospective and predictive approaches. Past deforestation patterns were analyzed using classified Landsat 5 and 7 imagery from 1984 to 2017. Pixel areas in hectares (ha) from land use land cover (LULC) classifications were used to detect land cover classes that were vulnerable to potential loss. The study also carried out a simple forest prediction using the simple moving averages (SMA) forecasting model based on the past and present deforestation patterns from LULC classification. The results showed that 3587.49 hectares (ha) of protected forest cover was converted into agricultural lands and barelands. In addition, 2532.96 hectares (ha) was converted from close forest to nonforest land cover from 2000 to 2017, which is equivalent to a 16% reduction in close forest cover within the FRs in the SWD. This loss was also 11% higher than close forest areas between 2000 and 2010. SMA forecasting showed that from 2017 to 2024, 877.38 hectares (ha) of close forest resources will convert to open forest resources and other nonforest land cover. Subtle accessibility routes such as navigable rivers and unofficial roads are the key instigators of protected forest clearance in the Sefwi Wiawso Forest District (SWFD). The SWFD is surrounded by many communities and is susceptible to uncontrollable biodiversity removal due to lack of proper monitoring of agricultural practices, mining operations, fuelwood collection, and illegal hunting, which represents a means of livelihood for the forest fringe community dwellers. The research serves as a benchmark for similar studies in efforts to investigate, measure, and project land cover change in protected forest areas.