Biological invasions threaten native biodiversity. Invasions that include reproductive interference, such as hybridization, can be especially detrimental to the persistence of native species. I investigated whether the decline of a North American vine, American bittersweet (Celastrus scandens), in the eastern portion of its native range is related to reproductive interference from an introduced congener, oriental bittersweet (C. orbiculatus). Also, I examined how anthropogenic factors, specifically commerce and alteration of biogeochemical cycles, may have contributed to the success of oriental bittersweet. I used field observation and genetic markers to survey individuals across the USA to determine the prevalence of wild hybrids, and to characterize invasion dynamics. Also, genetic markers tested the species identity of commercially available plants marketed as American bittersweet. Finally, I used experimental enrichment trials to simulate the elevated atmospheric carbon dioxide and increased nitrogen deposition expected in the future. The results suggest that human commerce, changing biogeochemical cycles, and especially reproductive interference played a role in the decline of the native vine and spread of the invasive congener in the past, and their influence will likely increase in the future.