Old herbarium specimens and historical floristic data give insight into regional floras for given time periods. They often cover historical time periods for which few other data are available. Herbaria thus allow the study of changes of the flora of a region across time. Using a 150-year-old regional herbarium together with a historical publication, we investigated to which extent the flora of the Swiss canton of Schaffhausen has changed, which habitats were particularly affected by local extinction, what the environmental requirements of extinct plants were and whether conclusions about the respective drivers such as land use change can be drawn. A total of 987 species were historically recorded in the study region of which 154 are currently no longer reported and are regionally extinct. This means that about one species disappeared from the region every year. Species that are currently in a high category of endangerment on the Swiss Red List have declined markedly in the canton of Schaffhausen, showing that Red Lists well portrait the endangerment of species. Looking at plant strategies, the more stress-tolerant and less competitive plants have disappeared. In addition, wetland, pioneer, ruderal and mountain species as well as agricultural weeds and light-demanding species showed highest extinction rates. In contrast, forest species had a low extinction rate, and species from fertilized meadows showed no decline. Our evaluation of a regional herbarium helps to inform nature conservation about particularly endangered habitats and possible drivers of species decline.