In view of past environmental degradation and anticipated climate change impacts, we assessed the potential for ecosystem-based adaptation in the Murray-Darling Basin, Australia. In a workshop with staff from three Catchment Management Authorities (CMAs) who had jurisdiction over three sub-basins, as well as technical experts, nine adaptation options were identified that ranged from environmental flows, restoring river channel habitat, reoperating infrastructure and controlling invasive species. A Catchment Adaptation Framework was developed and used to assess and compare these adaptation options with each of the CMAs, drawing on interviews with their key stakeholders, to identify the risks, benefits and costs. We found that ecosystem-based adaptation can augment catchment management programs and requires investment in a suite of different but complementary measures to lower risk. Our research found institutional challenges in implementing this approach, including the complexities of multi-agency management, constricting legal requirements, narrow funding arrangements, under-developed institutional capacity, difficulties of implementing catchment-scale programs on private property and the need to adhere to community expectations. These institutional issues are ubiquitous internationally and point to the wider issues of providing sufficient management capacity to support adaptation. The Catchment Adaptation Framework presented here enables river basin managers to systematically assess the adaptation options to better inform their decision-making.