Anthropological activities have contributed to high concentrations of greenhouse gases leading enormously to Global warming in the past decades. Such atmospheric changes are known to affect humans and ecological systems. One of the established anthropological activities to have increased greenhouse gasses is the depletion of vegetation cover which is a sink for CO2. In this study, remote sensing and geographical information systems were used to assess the effect of land use on vegetation cover and climate change over the last 20 years in greater Accra region of Ghana. Landsat images were stacked, rectified and classified into five land classes. Accuracy assessment of the classified images was assessed and change detection was determined. NDVI was used to validate vegetation change and variation in vegetation health over the study period. The study had an overall classification accuracy of 96.00%. Change detection statistics indicated that 12.07% and 22.92% vegetation cover increased, 25.84% and 13.98% vegetation cover decrease and 62.09% and 63.11% vegetation cover remained unchanged from 2002 to 2003 and 2003 to 2017 respectively. NDVI values from 2002 to 2017 ranged from 0.521127 to 0.506843 respectively indicating an 11.76% reduction in health of vegetation cover. The depletion and reduction in greenness of vegetation may have influence the high atmospheric CO2 concentration leading to 14 percent increase in temperature and periodic flooding of the study area over the last two decades.