12 Pags.- 6 Figs.- Data availability: Data will be made available on request. The Euro-Mediterranean region experienced a remarkable drought during the hydrological year 2021/22. Substantial and widespread impacts on water supply systems, agricultural crops, and the production of hydroelectric power were observed. This assessment characterises the drought from a long-term perspective using a multi-index approach and analyses the associated atmospheric circulation at the annual and monthly time scales. The main dynamical forcing of the drought was the unusual recurrence of high-pressure systems over western Europe, at least partly due to an anomalous southward shift in blocking activity and a remarkable occurrence of low-latitude blocks. This led to record-breaking positive geopotential height anomalies over western Europe and a poleward displacement of the North Atlantic eddy-driven jet. Although most of the region was affected by mild drought conditions, the 2021/22 event was not unprecedented in terms of precipitation deficits since other periods of the 20th century (e.g., in the 1920s, 1940s and 1970s) displayed moderate and severe drought conditions over larger areas. However, the 2021/22 drought has been the most intense since at least 1891 because of high atmospheric evaporative demand (AED) values associated with extreme temperatures, especially during the summer of 2022. This enhanced AED also contributed to depleting soil moisture and reducing runoff generation, leading to unprecedented deficits since at least 1965. Finally, we find important differences in the 2021/22 event as compared to other major historical droughts over the Euro-Mediterranean region. In particular, the contrasting effect of AED evidences its increasing role over the last decades and warns about the current risk of experiencing unprecedented droughts. This research work has received support from the European Commission – NextGenerationEU (Regulation EU 2020/2094), through CSIC's Interdisciplinary Thematic Platform Clima (PTI Clima) / Development of Operational Climate Services. SMV-S acknowledges funding by the research projects TED2021-129152B-C41, financed by the Spanish Ministry of Science and FEDER, and MEHYDRO (LINKB20080) financed by the i-LINK 2021 programme of CSIC. RMT was funded by the Portuguese Fundação para a Ciência e a Tecnologia (FCT) I.P./MCTES through national funds (PIDDAC) – UIDB/50019/2020 – Instituto Dom Luiz and project DHEFEUS - 2022.09185.PTDC. Peer reviewed