In the last decades, floods have increased in frequency all over the world due to diverse phenomena such as climate change, extended urbanization, land use, etc. Their social, cultural, economic and environmental impacts have also grown significantly, highlighting the need for the development of further studies and improved methods to manage and mitigate flood risk, mainly in urban areas. Historic sites need particular attention in this field, not only because the high and irreplaceable cultural value of these areas, but also taking into account that the constructive typologies that they host are particularly vulnerable to natural hazards. In consequence of that, the analysis of the phenomena, the evaluation of their consequences and the adoption of adequate mitigation and preparedness measures are presently a fundamental societal challenge. Having this in mind, the present paper aims at proposing an innovative methodology focused on the assessment of flood vulnerability in historic sites through the evaluation of a set of exposure and sensitivity indicators. From the analysis of these indicators, it is possible to obtain a Flood Vulnerability Index capable of measuring the spread of flood vulnerability over an extended area. The historic centre of Guimaraes, in Portugal, declared by UNESCO as a World Heritage Site in 2001, is used here as a pilot case study to apply and discusses the preliminary version of the approach. Although some improvements are still needed, this approach can be already used to provides preliminary vulnerability scenarios and to point the way to the definition of more efficient and customized strategies for managing and mitigating flood risk in historic sites. Moreover, with further improvements and calibrations resorting to larger and more diverse data, it will be possible to reduce some of the uncertainties currently involved in the assessment process and to make its application wider and more robust.