Mining-affected transboundary watersheds pose complex and often contentious challenges for researchers tasked with collecting data and/or providing scientific interpretations to inform policy and management decisions. How can scientific organizations overcome these challenges and collaborate to provide relevant and timely information for stakeholders? We will explore this question using a complex case example in the mining-affected transboundary Kootenai River Watershed. We will discuss strategies to overcome challenges and the potential opportunities for collaborative science. The transboundary Koocanusa Reservoir (also known as Lake Koocanusa) is within the international Kootenai (or “Kootenay” in Canada) drainage basin, is bisected by the border between the United States and Canada, and is impounded by Libby Dam upstream from Libby, Montana. Selenium concentrations have been measured by the USGS and others at concentrations above water-quality and aquatic-life standards in Koocanusa Reservoir. One source of selenium is waste rock and tailings storage from mining for metallurgical coal in the Elk River Valley, BC, Canada. In the absence of a central coordinating body, collaboration among international, Federal, State, local, and Indigenous governments has been complicated. Additionally, issues of data transparency and the lack of standardized data collection methodologies create inefficiencies for contributing agencies. Outspoken stakeholders, public opinion, and funding constraints often divert the central scientific endeavors and divide researchers in their efforts. These barriers can be overcome by a bilateral coordinating body chartered by the International Joint Commission or jointly by the US and Canadian Federal governments. Strategies for scientific collaboration that facilitate focused scientific efforts to answer the most relevant scientific questions in the absence of a unifying coordination body are discussed. Examples of proposed and successfully implemented partnerships with lessons learned are presented.