We combined field mapping, structural and microstructural analyses, stable‐clumped isotope geochemistry, and U‐Pb dating of calcite veins and syn‐tectonic slickenfibres, to assess the regional scale fault‐related fluid flow during the evolution of the External Hellenides fold‐and‐thrust belt. We show that fluid circulation during forebulge uplift was characterized by cold meteoric water‐derived fluids, from which calcite precipitated and sealed bed‐perpendicular joints likely formed during burial. Fluid circulation during foreland flexuring and early layer‐parallel shortening was characterized by warm fluids buffered by the carbonate host rock, which circulated through extensional faults and bed‐parallel veins. Mixing with meteoric‐derived fluids also occurred at this stage of tectonic evolution. Fluid circulation during the late stage of thrust wedge accretion and post‐orogenic extension at 1.6 ± 1 Ma was characterized by increasing dominance of cold meteoric water circulating in strike‐slip and normal faults. The ingress of external meteoric‐derived fluids was controlled by throughgoing fault conduits, while host rock‐buffered fluids were confined in isolated structures such as minor faults and veins. We developed a conceptual model of fault‐related fluid circulation, which invokes a transition from an open fluid system during forebulge uplift, to a semi‐closed fluid system during foreland flexuring and early layer‐parallel shortening, and to an open system during late thrust wedge accretion and post‐orogenic extension. This type of fluid circulation can have impact on fluid migration/leakage, including hydrocarbons, into or outside potential reservoirs in the highly prospective Hellenides‐Albanides fold‐and‐thrust belt, a renovated frontier for hydrocarbon exploration in the Mediterranean area.This article is protected by copyright. All rights reserved.