The increasing numbers and negative impacts of invasive species have prompted research on the relationship between human activities and the success of invasive horticultural plants. In this study, we use population genetic relationships to model the escape of a common garden vine, exotic Wisteria, into natural habitats. Urban and naturalized Wisteria populations in Charleston, South Carolina and Tallahassee, Florida were investigated using a combination of chloroplast, mitochondrial and nuclear DNA markers. Fifty-nine of 72 (81.9%) Wisteria collections were hybrids of Wisteria sinensis and W. floribunda. Chi-square analysis of the distribution of shared W. floribunda haplotypes among naturalized and urban populations supports the relationship of time with invasion success. Naturalized populations were more similar to those in historic neighborhoods. The most common haplotype, F1, was encountered 22 times but its distribution was not significantly different between urban and naturalized populations. In contrast, a significantly higher proportion of haplotype F2 found in naturalized populations suggests that selection may also be acting within these populations. Finally, due to extensive human dispersal, there is no relationship between genetic distance and geographical distance among the populations sampled. We conclude that Wisteria’s long history of horticulture, rampant hybridization, and human-aided dispersal are all implicated in the successful ability of these plants to invade natural habitats throughout the USA.