This article traces the emergence of a novel interpretive platform in EU politics, one that understands that an array of post-Great Recession changes in the global political economy are calling for a reassessment of the EU’s long-established approach to globalisation. The article argues that this rethinking is organised around the concept of “open strategic autonomy”, by which is meant an endeavour to reduce the EU’s external dependencies in a range of critical sectors. The article identifies the conceptual bases that inform the quest for strategic autonomy by examining the reforms prompted by this quest in industrial, competition, trade, digital, financial and defence policy. A conclusion arising from the analysis is that the relationship between European integration and global capitalism does not only concern the external policy domains of the EU, but also internal ones, in fact having key implications for the political economy of state intervention at the EU level.