The Benguela Current Large Marine Ecosystem (BCLME) is subject to moderate to high levels of fishing, mining and numerous other human pressures, all of which are set to intensify through current socio-economic development initiatives in Angola, Namibia and South Africa. There is, however, minimal spatial protection of marine and coastal ecosystems in the region, potentially reducing the sustainability of the planned development and the likelihood of achieving Sustainable Development Goals. As a precursor to Marine Spatial Planning (MSP) processes in the three countries, and to guide establishment of Marine Protected Areas (MPAs), this study aimed to: assess two headline indicators of ecosystem status, namely their potential threat status and current spatial protection levels; and to use Systematic Conservation Planning (SCP) to prioritise specific areas for protection to achieve networks of MPAs that are representative of national and regional biodiversity. Two hundred and forty eight ecosystem types in the coastal (n = 134), offshore benthic (n = 86) and pelagic (n = 28) zones of the BCLME were classified, mapped and assessed. Overall, 35% of all ecosystem types in the study domain were threatened, with more threatened coastal (37%) and offshore benthic (37%) ecosystem types compared to pelagic ecosystem types (14%), although the same pattern was not necessarily evident within each country. Nearly two thirds (59%) of the BCLME ecosystem types were not protected in MPAs, and most of those that were well (19%) or moderately protected (14%) were coastal types that are within a single extensive MPA in Namibia. Notwithstanding, there was still a sufficient area of most ecosystem types that was assessed to be in good ecological condition in all three countries and that could be prioritised for representative protection of the region's biodiversity. A portfolio of priority conservation areas was identified from Marxan selection-frequency outputs, providing a spatial vision for protected areas in the BCLME that includes coastal, inshore and offshore areas in all three countries. This first assessment of marine ecosystem threat and protection status for an entire LME demonstrates a rapid science-based approach that can inform integrated ocean management and multiple development goals. The study provides a basis for identifying Ecologically or Biologically Significant Marine Areas, potential sites for MPAs or other spatial management in the region, and demonstrates the contribution of SCP and spatial management to MSP.