The global health burden due to physical inactivity is enormous and growing. There is a need to consider new ways of generating evidence and to identify the role of government in promoting physical activity at the population level. In this paper, we summarize key findings from a large-scale cross-national collaboration to understand physical activity promotion in Brazil. We describe the main aspects of the partnership of Project GUIA (Guide for Useful Interventions for Activity in Brazil and Latin America) that sustained the collaborative effort for eight years and describe how the evidence gathered from the collaboration triggered political action in Brazil to scale up a physical activity intervention at the national level. Project GUIA is a cross-national multidisciplinary research partnership designed to understand and evaluate current efforts for physical activity promotion at the community level in Latin America. This example of scaling up is unprecedented for promoting health in the region and is an example that must be followed and evaluated.