Deconstructing the drivers of large-scale vegetation change is critical to predicting and managing projected climate and land use changes that will affect regional vegetation cover in degraded or threated ecosystems. We investigate the shared dynamics of spatially variable vegetation across three large watersheds in the southern Africa savanna. Dynamic Factor Analysis (DFA), a multivariate time-series dimension reduction technique, was used to identify the most important physical drivers of regional vegetation change. We first evaluated the Advanced Very High Resolution Radiometer (AVHRR)- vs. the Moderate Resolution Imaging Spectroradiometer (MODIS)-based Normalized Difference Vegetation Index (NDVI) datasets across their overlapping period (2001–2010). NDVI follows a general pattern of cyclic seasonal variation, with distinct spatio-temporal patterns across physio-geographic regions. Both NDVI products produced similar DFA models, although MODIS was simulated better. Soil moisture and precipitation controlled NDVI for mean annual precipitation (MAP) < 750 mm, and above this, evaporation and mean temperature dominated. A second DFA with the full AVHRR (1982–2010) data found that for MAP < 750 mm, soil moisture and actual evapotranspiration control NDVI dynamics, followed by mean and maximum temperatures. Above 950 mm, actual evapotranspiration and precipitation dominate. The quantification of the combined spatio-temporal environmental drivers of NDVI expands our ability to understand landscape level changes in vegetation evaluated through remote sensing and improves the basis for the management of vulnerable regions, like the southern Africa savannas. Full article