European buildings are producing a massive amount of data from a wide spectrum of energy-related sources, such as smart meters’ data, sensors and other Internet of things devices, creating new research challenges. In this context, the aim of this paper is to present a high-level data-driven architecture for buildings data exchange, management and real-time processing. This multi-disciplinary big data environment enables the integration of cross-domain data, combined with emerging artificial intelligence algorithms and distributed ledgers technology. Semantically enhanced, interlinked and multilingual repositories of heterogeneous types of data are coupled with a set of visualization, querying and exploration tools, suitable application programming interfaces (APIs) for data exchange, as well as a suite of configurable and ready-to-use analytical components that implement a series of advanced machine learning and deep learning algorithms. The results from the pilot application of the proposed framework are presented and discussed. The data-driven architecture enables reliable and effective policymaking, as well as supports the creation and exploitation of innovative energy efficiency services through the utilization of a wide variety of data, for the effective operation of buildings.