Freshwater ecosystems in southern Africa are globally significant yet under-represented in conservation planning. The headwaters of the Cubango, Cuito, Cuando, and Lungué-Vungo rivers in southeastern Angola form the source of the Okavango and Zambezi systems, sustaining downstream ecosystems and wetlands of international importance. Despite their ecological value, these catchments face escalating pressures from land conversion, fire, and infrastructure development, alongside climate-induced hydrological shifts. To provide guidance on freshwater conservation priority areas, we applied a systematic conservation planning framework using Marxan software across ~320,000 km² of the Angolan headwaters. The analysis integrated 178 hydro-ecological features (fish, birds, mammals, wetlands, river types, and peatlands) under four cost scenarios reflecting human pressure and hydrological connectivity. Results consistently highlighted the upper Cuito and Cuando rivers, the Cubango headwaters, and the Lungué-Vungo catchment as critical areas supporting high aquatic biodiversity, intact peatland systems, and longitudinal connectivity. Stakeholder validation workshops identified these as focal zones for conservation investment and policy alignment. The recommended ”Human Footprint” cost scenario offers a pragmatic balance between ecological representation and implementation feasibility in a region with limited infrastructure and ongoing development. The study demonstrates the feasibility of applying spatial prioritization tools in data-limited, post-conflict landscapes, providing a replicable approach for guiding national freshwater conservation planning in Angola and contributing to regional biodiversity and climate resilience objectives.