Five species of Inocybe from eastern North America are described as new: Inocybe carolinensis, Inocybe dulciolens, Inocybe friabilis, Inocybe glaucescens, and Inocybe vinaceobrunnea. Inocybe carolinensis is a new species in Inocybe sect. Inocybe; I. dulciolens and I. glaucescens are two new species in Inocybe sect. Lactiferae; I. friabilis is described as new in the Pseudosperma clade (Inocybe sect. Rimosae sensu stricto); and I. vinaceobrunnea is newly described for I. jurana sensu Hesler in the Inosperma clade (Inocybe sect. Rimosae sensu lato). At least four of the five species are endemic to regions of eastern North America based on current distribution data. ITS, 28S rDNA, rpb2, and rpb1 genes, in combination with morphological and ecological traits, are used to aid in species recognition. Phylogenetic trees, taxonomic descriptions, and illustrations are provided.