Exotic plant invasion, a global issue, has a tremendous impact on ecology, economy, human, and animal health. Alligator weed (the world’s first aquatic weed) is a serious invasive weed in 32 different countries of South America, Australia, Asia, and North America. Recently, it has been recorded as a threat weed of rice, maize, soybean, vegetables, fruit trees, and pastures, causing 19–45% yield losses in these crops in addition to its infestation in canals, lakes, and ditches. Alligator weed has the potential to ruin agricultural and natural ecosystems and recreational areas. Ability to propagate via vegetative fragmentation, water-borne dispersal of vegetative propagules, and allelopathic potential contribute towards its success as an invasive weed species of terrestrial, semi-aquatic, and aquatic environments. Application of glyphosate, metsulfuron-methyl, dichlobenil, fluridone, hexazinone, triclopyr amine, dimethylamine, imazapyr, diuron, and amitrole herbicides have been found most effective in controlling this weed in different habitats. Agasicles hygrophila, Vogtia malloi pastana, Amynothrips andersoni, and Nimbya alternanthera have been reported as bio-agents for the control of alligator weed. We present a comprehensive review of the biology, interference, and management options of an extremely dangerous invasive weed species. Although management of alligator weed through chemical, biological, and mechanical means are often effective, there is need for well-planned, long-term field experiments to evaluate the role of different factors that are stated to be responsible for its increasing infestation and distribution (e.g., regeneration after damage caused by herbicides, high soil fertility levels, soil disturbances, shallow vs. deep ploughing and grazing management). It is recommended that future research should focus more on the integration of different management approaches in both aquatic and terrestrial ecosystems, and in various ecological regions.