The federalisation processes of US and EU financial supervision have both originally been founded on similar—although not identical—legal bases: regulating interstate commerce in the US (US Const., Art. 1, Sect. 8, Cl. 3) and establishing or ensuring the functioning of the internal market in the EU (Art. 114 TFEU). The complexity of the US system, comprised of a patchwork of state and federal authorities mainly established in the first part of the twentieth century, is the product of both major economic failures and a specific political culture. The progressive federalisation of financial supervision within the EU is the result of a well-thought-out project of integration of the internal market. The last financial crisis and the recognition of the overarching objective of financial stability have nonetheless led to significant evolutions, more particularly through the establishment of the three European supervisory authorities (ESAs). Moreover, and perhaps more importantly, the latest initiatives related to the establishment of an EU Banking Union have profoundly transformed the underpinnings of financial supervision in the EU since it is, from this point forward, partially linked with the Economic and Monetary Union (EMU) process. Within this framework, the purpose of this contribution is to explore how political and legal differences between the EU and US systems have shaped and influenced the structures and institutional aspects of supervision on both parts of the Atlantic without necessarily leading to significant divergences as to the contents of financial regulation. More specifically, a comparative study of these two systems highlights significant differences as to the interplay between federal and State supervisors.