Analysis of ITS sequence data showed unexpected complexity for Eupatorium album and E. petaloideum, a closely related species pair from eastern North America that has been considered to form a single species. The two species consistently differed in ITS sequence by seven to eight bp as well as a one bp indel, and detailed analysis revealed little intraspecific variation. The ITS sequences of other samples that had similar but slightly differing morphology and were pollen sterile gave several patterns involving bp or indel polymorphisms that indicated that they were of hybrid derivation. Based on differences in leaf and phyllary shape and glandular trichome distribution it was possible to delimit the individual hybrid combinations from one another and from their progenitor species. Material previously called E. album from the western part of its range is of hybrid origin from E. album and E. lancifolium, and is described here as Eupatorium sullivaniae. Material from the northeastern part of the range previously called E. album var. subvenosum is a hybrid derivative of E. petaloideum and E. hyssopifolium, elevated here to Eupatorium subvenosum. Samples having the general morphology previously associated with E. album var. vaseyi included hybrid derivatives of the combinations E. petaloideum/E. sessilifolium, here reinstated as E. vaseyi, and E. petaloideum/E. sessilifolium/E. perfoliatum, here reinstated as E. fernaldii. Other samples gave ITS sequence data consistent with a derivation from E. album/E. hyssopifolium. The species of hybrid derivation have geographic ranges that extend beyond those of the inferred progenitors, in the case of E. subvenosum involving a disjunction of several hundred kilometers, suggesting that there have been considerable differences in species ranges over time.