The European Union is charting a strategic path to becoming the first climate-neutral continent by 2050, grasping the opportunities of the digital age, building an economy that works for people, promoting the European way of life, strengthening our unique brand of responsible global leadership, and nurturing, protecting and strengthening our democracy. Openness, as well as rules-based international and multilateral cooperation, are strategic choices. They stimulate prosperity, fairness, stability, competitiveness and dynamism within the EU and beyond. The history of the European project demonstrates the benefits of well-managed interdependence and open strategic autonomy based on shared values, cohesion, strong multilateral governance and rules-based cooperation. The pandemic has only strengthened the case for international cooperation to address global challenges. This 2021 Strategic Foresight Report presents a forward-looking and multi-disciplinary perspective on the EU’s capacity and freedom to act in the coming decades. Based on an expert-led, cross-sectoral foresight process, it presents global trends, uncertainties and choices that will shape Europe’s future. The report provides the context for possible policy responses. It builds on the 2020 Strategic Foresight Report, which introduced resilience as a new compass for EU policymaking. Section II identifies important structural global trends towards 2050 that will affect the EU’s capacity and freedom to act: climate change and other environmental challenges; digital hyperconnectivity and technological transformations; pressure on democracy and values; shifts in the global order and demography. Section III sets out ten areas in which the EU could strengthen its open strategic autonomy and global leadership. The report stresses that the EU’s future capacity and freedom to act will depend on whether the EU is able to make ambitious choices today, guided by its values and interests, across the identified policy areas.