Scenario analysis can be a useful tool to explore paths to a desirable future. This paper is a ‘future history’ describing the how stakeholders in the Great Lakes–St. Lawrence River basin of North America rallied to confront regional challenges 50 years into the future (2013–2063). This future scenario was developed by considering how nine drivers of change (aquatic invasive species; biological and chemical contaminants; climate change; demographics and societal values; economy; energy; governance and geopolitics; water quantity; and technology) might impact the region. This “thriving and prosperous” scenario envisions that in the beginning, Great Lakes residents, scientists, and policymakers saw “the writing on the wall,” recognizing that past approaches to environmental policy failed to provide long-term environmental, social, and economic prosperity. In response, policymakers in the Great Lakes region began formulating and implementing new policies, but actions were scattered across the region and uncoordinated across geopolitical boundaries. Recognizing the need to coordinate their efforts, Great Lakes stakeholders began “marching in step” by agreeing on a common set of guiding principles for future policy actions. Building on this momentum, Great Lakes policymakers implemented a suite of regulations and initiatives that recognized the Great Lakes region as a complex social–ecological system. Between 2053 and 2063, the region began to reap the benefits of coordinated policy action. By 2063, the Great Lakes region showed how a long-term commitment to improving the environment can sustain a thriving and prosperous ecosystem and economy.