The Ranger uranium mine is surrounded by the World Heritage Kakadu National Park, Australia, and is upstream of the Ramsar-listed wetlands of the Magela Creek floodplain. We present the results of a Quantitative Ecological Risk Assessment (QERA) for the floodplain that combines both point source mining risks and diffuse non-mining landscape-scale risks. A high level of protection for the biodiversity of aquatic ecosystems was used as the assessment endpoint. Mining risks in the surface water pathway were assessed for four key mine-associated solutes (uranium, manganese, magnesium, and sulphate), and non-mining landscape-scale risks were assessed for weeds, feral pig damage, unmanaged dry season fire, and saltwater intrusion from potential sea-level rise due to climate change. Results show that non-mining landscape-scale risks are currently several orders of magnitude greater than risks from mine water contaminants. A weed (Para grass; Urocloa mutica) is the major ecological risk because of its extent, effect, and rapid spread rate. The QERA was incorporated into a Bayesian Belief Network to help evaluate different management strategies. We conclude that non-mining landscape-scale risks to the floodplain should receive the same level of close scrutiny and investment as that applied to uranium mining risks.