We examined changes in the native vascular flora of Franklin County, Massachusetts, a largely rural county with a long history of botanical investigation. The historical flora was documented using herbarium specimens and literature records, and the current flora was assessed in 10 years of field work starting in 2010. The county contains 26 towns, and apparent changes were based on town-level presence/absence. In total, 1205 species were recorded. Apparent losses from the historical flora totaled 5.6% of species, and apparent gains totaled 4.2%. Several families exhibited greater declines than the flora as a whole, including the Orchidaceae, Ophioglossaceae, Ranunculaceae, and Violaceae. Species dependent on fungi during at least part of their life cycle declined relative to other species, but were concentrated in a small group of families, including the Orchidaceae and Ophioglossaceae. Species with fleshy fruits increased relative to those with ant-dispersed seeds. Annuals increased relative to biennials and perennials, probably due to the increasing extent of ruderal habitats. Graminoids showed greater apparent increases than forbs, which may reflect undercollecting of the former taxa during the historical period. Species changes were related to habitat, with marked increases in plants of ruderal habitats, but other apparent changes may reflect sampling biases. Northern taxa appear to be declining relative to other species, particularly in towns at lower elevations. This study is one of several that have examined floristic changes in the northeastern United States and is part of a nascent literature suggesting that climate changes have altered the southern New England flora in the past century. Additional documentation of regional floras is needed to facilitate assessments of future floristic changes.