Operational monitoring of vegetation and its response to climate change involves the use of vegetation indices (VIs) in relation to relevant climatic data. This study analyses the temporal variations of vegetation indices in response to climatic data (temperature and precipitation) to better understand the phenological changes in the Wa-West and Tolon districts of Ghana during 1999–2011. This study also examines the inter-annual variation of vegetation indices and lag effects of climate variables (temperature and precipitation) using simple regression and correlation approaches. Results indicate that the mean Normalized Difference Vegetation Index (NDVI) and Normalized Difference Soil Index (NDSI) were signiﬁcantly correlated with the mean temperature, whereby the value of NDVI increases with a decrease in temperature and value of NDSI increases with an increase in temperature. On examining seasonal variations, our ﬁndings indicated that the months of August and September have the highest mean NDVI values. This study conﬁrms that consistently rising temperature and altered precipitation patterns have exerted a strong inﬂuence on temporal distributions and productivities of the terrestrial ecosystems of the Tolon and Wa-West districts of Ghana. Furthermore, this research demonstrates how vegetation indices can be used as an indicator to monitor phenological changes in the terrestrial ecosystem.