A rapid increase in the world’s population over the last century has triggered the transformation of the earth surface, especially in urban areas, where more than half of the global population live. Ghana is no exception and a high population growth rate, coupled with economic development over the last three decades, has transformed the Greater Accra region into a hotspot for massive urban growth. The urban extent of the region has expanded extensively, mainly at the expense of the vegetative cover in the region. Although urbanization presents several opportunities, the environmental and social problems cannot be underestimated. Therefore, the need to estimate the rate and extent of land use/land cover changes in the region and the main drivers of these changes is imperative. Geographic Information Systems (GIS) and remote sensing techniques provide effective tools in studying and monitoring land-use/land-cover change over space and time. A post classification change detection of multiple Landsat images was conducted to map and analyse the extent and rate of land use/land cover change in the region between 1991 and 2015. Subsequently, the urban extent of the region was forecasted for the year 2025 using the Markov Chain and the Multi-Layer Perceptron neural network, together with drivers representing proximity, biophysical, and socio-economic variables. The results from the research revealed that built-up areas increased by 277% over the 24-year study period. However, forest areas experienced massive reduction, diminishing from 34% in 1991 to 6.5% in 2015. The 2025 projected land use map revealed that the urban extent will massively increase to cover 70% of the study area, as compared to 44% in 2015. The urban extent is also anticipated to spill into the adjoining districts mainly on the western and eastern sides of the region. The success of this research in generating a future land-use map for 2025, together with the other significant findings, demonstrates the usefulness of spatial models as tools for sustainable city planning and environmental management, especially for urban planners in developing countries.