Cropland expansion to meet the growing demand for food and fuel is a driving factor in forest degradation. Over the next few decades, increases in the area of agricultural land are expected to be concentrated in sub-Saharan Africa, which still has large tracts of unexploited land suitable for agricultural production. We analyzed land-cover change in northern Ghana between 1984 and 2015 and compared it with background social factors associated with land change. Maps from three points in time were analyzed to identify the impact of cropland expansion on the distribution of natural vegetation. Three-level intensity analysis revealed that the overall rate of change for the 31-year period was less than that of the first time interval (1984–1999); however, the overall impact on natural vegetation was substantial, and grassland in particular was reduced to a very small proportion of the area over the period. Cropland replaced only grassland during the first time interval, but also began to replace open woodland during the second interval (1999–2015). The in-depth assessment revealed that cropland expansion continued at a steady rate, but the impact on natural vegetation was not uniform across vegetation types; grassland was more vulnerable than woodland, and woodland became increasingly targeted with continual expansion of the agricultural frontier as population increased. Further validation of the socio-cultural factors associated with the observed transitions will help to identify the explicit implications and assist in developing strategies to minimize the impacts of land-use change on regional livelihoods.