A long-standing and unresolved issue in invasion biology concerns the rapid adaptation of invaders to nonindigenous environments. Mikania micrantha is a notorious invasive weed that causes substantial economic losses and negative ecological consequences in southern China. However, the contributions of gene flow, environmental variables, and functional genes, all generally recognized as important factors driving invasive success, to its successful invasion of southern China are not fully understood. Here, we utilized a genotyping-by-sequencing approach to sequence 306 M. micrantha individuals from 21 invasive populations. Based on the obtained genome-wide single nucleotide polymorphism (SNP) data, we observed that all the populations possessed similar high levels of genetic diversity that were not constrained by longitude and latitude. Mikania micrantha was introduced multiple times and subsequently experienced rapid-range expansion with recurrent high gene flow. Using FST outliers, a latent factor mixed model, and the Bayesian method, we identified 38 outlier SNPs associated with environmental variables. The analysis of these outlier SNPs revealed that soil composition, temperature, precipitation, and ecological variables were important determinants affecting the invasive adaptation of M. micrantha. Candidate genes with outlier signatures were related to abiotic stress response. Gene family clustering analysis revealed 683 gene families unique to M. micrantha which may have significant implications for the growth, metabolism, and defense responses of M. micrantha. Forty-one genes showing significant positive selection signatures were identified. These genes mainly function in binding, DNA replication and repair, signature transduction, transcription, and cellular components. Collectively, these findings highlight the contribution of gene flow to the invasion and spread of M. micrantha and indicate the roles of adaptive loci and functional genes in invasive adaptation.