Banana production landscapes in the African Great Lakes Region (AGLR) have been under immense pressure from Xanthomonas wilt (XW) disease over the past two decades. XW, first reported on banana in central Uganda and eastern DR Congo in 2001, has since spread to the entire AGLR. XW is currently spreading westwards from hot spots in eastern DR Congo highlands, putting the plantain (Musa AAB genome) belt of central and west Africa at risk. In-depth understanding of the key variables responsible for disease spread, current hotspots, and vulnerable landscapes is crucial for disease early warning and management. We mapped aggregated disease distribution and hotspots in the AGLR and identified vulnerable landscapes across African banana production zones. Available data on disease prevalence collected over 11 years was regressed against environmental and expert developed covariates to develop the AGLR XW hotspots map. For the Africa-wide risk map, precipitation, distance to hotspots, degree of trade in fresh banana products, production zone interconnectedness and banana genotype composition were used as covariates. In the AGLR, XW was mainly correlated to precipitation and disease/banana management. Altitude and temperature had unexpectedly low effects, possibly due to an overriding impact of tool-mediated spread which is part of the management covariate. In the AGLR, the eastern part of DR Congo was a large hotspot with highest vulnerability. Apart from endemic zones in the AGLR and Ethiopia, northern Mozambique was perceived as a moderate risk zone mainly due to the predominance of ‘Bluggoe’ (Musa ABB type) which is highly susceptible to insect-vectored transmission. Presence of XW hotspots (e.g. eastern DR Congo) and vulnerable areas with low (e.g. north-western Tanzania) or no disease (e.g. Congo basin, western DR Congo and northern Mozambique) pressure suggest key areas where proactive measures e.g. quarantines and information sharing on XW diagnosis, epidemiology, and control could be beneficial.