Diadromous fishes have drastically declined over the last century, especially in Europe. Several authors have highlighted the role of large dams in this decline, but in fact, its causes are potentially multiple and cumulative, including degradation of local environmental conditions and widespread fragmentation of hydrographic networks associated with the pervasive establishment of smaller barriers. Consequently, there is a need to improve the identification and prioritization of the drivers of diadromous species loss in order to identify and apply the most appropriate conservation and restoration measures. In this study, we used both historical sources (from mid-18th to early 20th century) and current data to quantify the long-term loss of diadromous taxa over 555 sites throughout the French river network. Then, we modeled the effects of several anthropogenic pressures (e.g. barriers, water quality, hydrological and river morphological alterations) on diadromous taxon loss. Lastly, we assessed the potential consequences of four different scenarios of anthropogenic pressure reduction. Due to uncertainties in historical sources, some species were grouped into taxa leading to a potential underestimation of actual species extinctions. Despite this limitation, our results showed that the decline in diadromous assemblages is widespread but with contrasting magnitudes depending on site locations. The maximum height and density of barriers appeared as the major factors of taxon loss. Over the scenarios tested, we observed that exclusively improving local conditions have much more limited effects than restoring river continuity. Focusing actions on large dam removal did not show the strongest responses compared to removing medium and small-sized barriers. For effective and sustainable restoration of diadromous fish assemblage, (1) historical occurrences of diadromous fishes should be used as an indicator for assessing recovery, and (2) undertaken measures must be adapted to each basin to target and limit the number of barriers to remove while allowing diadromous fish recovery.