Globally, giant miscanthus (Miscanthus × giganteus J.M. Greef & Deuter ex Hodkinson & Renvoize [sacchariflorus × sinensis]) is used as a biofuel crop due to its ability to persist in a wide range of climates. However, little work has assessed this plant's ability to invade and persist in wetland habitats. In outdoor mesocosms, we examined M. × giganteus's ability to grow in simulated wetland versus upland habitats and examined chemical control strategies for both habitats using aquatic-labeled herbicides. Miscanthus × giganteus growth was consistently greater in simulated wetland habitats, with wetland plants 2.4 to 3 times taller than upland plants at 6 wk after treatment (WAT) and 2.8 to 3.3 times taller than upland plants at 12 WAT. Miscanthus × giganteus aboveground biomass was 12.7 to 17.7 times greater in wetland-versus upland-grown plants at 6 WAT and 9.6 to 12.5 times greater at 12 WAT. Belowground biomass was 4.5 to 10.7 times greater in wetland versus upland grown plants at 6 WAT and 4.0 to 6.1 times greater at 12 WAT. Miscanthus × giganteus belowground biomass was always greater than aboveground in both habitats at 6 (6.0 times greater in wetlands and 2.9 times greater in uplands) and 12 WAT (3.8 times greater in wetlands and 1.3 times greater in uplands). Generally, all herbicide treatments reduced M. × giganteus height (66% to 100% reduction) and biomass (84% to 100%) compared with nontreated plants at 12 WAT; however, glyphosate (5,716.3 g ai ha^–1) and imazapyr (1,120.8 g ai ha^–1) performed better than imazamox (560.4 g ai ha^–1) and penoxsulam (98.6 g ai ha^–1). This is the first work to provide evidence that M. × giganteus can be chemically controlled in wetland habitats. Furthermore, this is the first work to show that penoxsulam (an acetolactate synthase–inhibiting herbicide) can reduce M. × giganteus growth in upland or wetland habitats.