Skunk-vine (Paederia foetida L.) is an invasive vine native to eastern and southern Asia and is widely distributed in Florida, Hawaii, and other southeastern U.S. states; however, little research has focused on herbicide control. Greenhouse and field experiments were conducted to determine efficacy of aminocyclopyrachlor, aminopyralid, fluroxypyr, glyphosate, imazapic, triclopyr amine, and triclopyr ester at low and high labeled rates when foliar applied to P. foetida at various growth stages in greenhouse experiments. Longer-term control was evaluated in field experiments in central Florida using the same herbicides. PRE herbicides labeled for use in landscape plantings, including dimethenamid-P, flumioxazin, indaziflam, isoxaben, and prodiamine, were also evaluated in greenhouse trials by seeding containers with P. foetida seed. In greenhouse experiments, POST herbicides, including aminocyclopyrachlor, aminopyralid, glyphosate, both triclopyr formulations, and the high rate of fluroxypyr (0.24 kg ae ha−1), provided >90% control across all growth stages at 4 mo after treatment with no regrowth observed. Imazapic provided 49% to 89% control, with efficacy decreasing with P. foetida size, and generally provided less control than other treatments. Field experiments confirmed results from greenhouse studies. In PRE trials, flumioxazin and prodiamine provided better control than all other PRE herbicides evaluated, reducing shoot weights by 99% and 84%, respectively, compared with nontreated controls. Our data suggest all herbicides evaluated POST could potentially be used to manage P. foetida, although less control was achieved with imazapic compared with other herbicides. Further research is needed to determine herbicide efficacy on more mature plants and to develop application methods that would be less injurious to non-target vegetation. In landscapes, flumioxazin or prodiamine could be used for PRE control, but POST options that are labeled for landscape use should be identified in future research.