This study describes the principal changes in the flora of the Cayuga Region over the past 200 years. The region's flora has been thoroughly documented by botanists at different times but the changes have not before been synthesized. The region studied is approximately 10,000 km² surrounding Ithaca, NY, USA. The plant diversity of the Cayuga Region of New York has increased substantially over the past two centuries, as the gains of non-native plant species have far outnumbered the losses of natives. Of 1,265 vascular plant species native to the region, only 43 have been lost, despite large changes in land use and habitat areas. None of the species losses represent global extinction. There are no clear correlates or predictors for the species that disappeared. They were not all rare, nor were they predominantly in one kind of habitat, or from particular plant families. The majority of the 777 non-native plant species in the extant flora are rare or scarce within the Cayuga Region, and only a small number are of concern as aggressive invaders. Most of the non-natives are Old World herbaceous species of open, unforested habitats.