With Brexit, the European Union has entered the first phase of unprecedented and potentially wider political disintegration. This is a reflection of the growing division between the EU’s core political agenda, defined under Germany’s increasingly uncompromising hegemonial leadership throughout the past decade, and the political preferences of the periphery in Southern and Central-Eastern Europe. This article critically examines the multiple effects of Germany’s dominant leadership role in the EU since the onset of the Eurozone sovereign debt crisis on the basis of a liberal intergovernmentalist perspective. It also considers future perspectives for German leadership in the EU after Brexit. As Angela Merkel enters her fourth term as German chancellor, she faces growing domestic political pressures and dwindling support for German leadership in the EU. German leadership is therefore more constrained than ever at a time when it is urgently needed to steer the EU away from further disintegration and towards lasting consolidation. The latter will require Berlin to engage profoundly in rebuilding a multilateral EU leadership constellation with France and Poland, which develops an inclusive policy agenda that represents the growing diversity of national interests amongst the remaining EU-27 member states.