Mile-a-minute (Mikania micrantha Kunth) is a tropical American species and has become a worldwide invasive weed. It was first introduced to mainland China in 1983 in Yingjiang City, Dehong State, Yunnan Province. To assess the origins of populations from Dehong State, Yunnan Province, the genetic structure of 427 individuals from 11 M. micrantha populations from Yunnan, Guangxi, Hainan, and Guangdong provinces were analyzed. A total of 28 alleles were detected in 12 nuclear microsatellite loci. Genetic diversity at the population level was relatively high. An analysis of molecular variance showed that most of the variation occurred within populations (82.73%), and only 18.27% occurred among populations. The genetic differentiation coefficient (F_ST) was 0.183. The estimated gene flow (N_m) from F_ST was 1.116. The independent origins of four populations collected from Dehong State, Yunnan Province, was determined by the unweighted pair-group method with arithmetic means clustering and STRUCTURE analysis. Three gene clusters and one admixture gene cluster were found. A Mantel test of pairwise Nei's genetic distances and pairwise geographic distances revealed no evidence for isolation by distance (r = 0.068, P = 0.343). These results suggest that the post-introduction admixture caused by multiple introductions and high gene flow might contribute to the evolutionary adaptation of M. micrantha. These results could provide a scientific basis for the management of invasive M. micrantha.