Drought caused by climate change has significantly increased vegetation vulnerability in Afghanistan during the last decades. This paper investigates vegetation response to drought at multiple scales across the country based on historical data from 1980 to 2020. It explores the multiscale relationships between drought as indicated by the grid-based standardised precipitation evapotranspiration index (SPEI) and vegetation condition as represented by the satellite-derived vegetation anomaly index (VAI). It also examines the links of dominant land cover with drought and their implications for agriculture. We assess the spatiotemporal correlations by integrating TerraClimate grids with timeseries data sourced from NOAA AVHRR (National Oceanic and Atmospheric Administration Advanced Very High-Resolution Radiometer), MODIS (Moderate Resolution Imaging Spectroradiometer) images and ESA CCI (European Space Agency Climate Change Initiative) land cover maps. We evaluated the effect of cumulative drought on predominant land covers. Our results show years 2000–2001 and 2017–2018 as the driest in the last four decades, and vegetation substantially correlated to drought with spatial and temporal variations across Afghanistan. The most sensitive vegetation response months are June to July and the most significant cumulative drought impacts on vegetation are 6 to 8 months. The predominant land covers more prone to negative effects under severe drought are (in order) shrubland, rainfed cropland, grassland, trees, and irrigated cropland. These findings suggest the sensitivity of vegetation to drought that future national scale drought management should be focused on. This study also demonstrates the usefulness of open-access data to researchers and planners in data-poor countries.