The Stephen West Williams Herbarium, an important early collection of plants from western Massachusetts, is in the Henry N. Flynt Library of Historic Deerfield. Most of the plants in the herbarium were collected between 1816 and 1818 in Deerfield, Franklin County, Massachusetts. The herbarium had apparently never been systematically examined by contemporary botanists prior to our work. The 390-page herbarium contains 556 specimens representing 453 species, 74% of which are native and 26% introduced. Eight of the native species in the herbarium are now considered rare in Massachusetts. Reflecting Williams' interest, about half the specimens in the collection had a medicinal use. Intensive floristic surveys in Deerfield between 1944 and 2015 failed to find 64 (14%) of the species collected by Williams, including about 4% of the native and 42% of the introduced species. The specimens establish a pre-1820 date for the presence of at least 90 introduced species that are currently considered naturalized in Massachusetts. The collection also provides documentation for 34% of the vascular plants in Edward Hitchcock's 1829 “Catalog of Plants Growing without Cultivation in the Vicinity of Amherst College,” the first flora for the Connecticut River Valley of Massachusetts.